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A detailed understanding of pancreatic β-cell mass distribution is a key element to fully appreciate the pathophysiology of models of diabetes and metabolic stress. Commonly, such assessments have been performed by stereological approaches that rely on the extrapolation of two-dimensional data and provide very limited topological information. We present ex vivo optical tomographic data sets of the full β-cell mass distribution in cohorts of obese ob/ob mice and their lean controls, together with information about individual islet β-cell volumes, their three-dimensional coordinates and shape throughout the volume of the pancreas between 4 and 52 weeks of age. These data sets offer the currently most comprehensive public record of the β-cell mass distribution in the mouse. As such, they may serve as a quantitative and topological reference for the planning of a variety of in vivo or ex vivo experiments including computational modelling and statistical analyses. By shedding light on intra- and inter-lobular variations in β-cell mass distribution, they further provide a powerful tool for the planning of stereological sampling assessments.

The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age. Our data show that cystic lesions constitute a significant volume of the hyperplastic ob/ob islets. We propose that these lesions are formed by a mechanism involving extravasation of red blood cells/plasma due to increased islet vessel blood flow and vessel instability. Further, our data indicate that the primary lobular compartments of the ob/ob pancreas have different potentials for expanding their β-cell population. Unawareness of the characteristics of β-cell expansion in ob/ob mice presented in this report may significantly influence ex vivo and in vivo assessments of this model in studies of β-cell adaptation and function.

The technology and the first experience of the local cryotherapy for tumors of the breast, lateral triangle of the neck and lumbar area using ultrasound navigation of cryoprobes and new medical equipment are presented.

Ultrasound scan allows determining tumor border in the area of inflammatory infiltrate, creating a three-dimensional plan of the operation, performing accurate pointing injecting cryoprobes as well as managing a monitor of cryoablation. As a result the frequency of repeated recurrences of infected recurrent tumors in difficult anatomical areas of the face decreased to 4%.

The paper presents the results of a study of the ovarian reserve in young women who received treatment for malignant tumors in childhood and adolescence and are in complete clinical remission. The function of the reproductive system was evaluated by serum concentrations of gonadotropins, estradiol, anti-Müllerian hormone (AMH) and inhibin B. The results were compared to the treatment, patients' age at the beginning of therapy and at the time of the examination. AMH level in serum was the most informative indicator of ovarian reserve in patients treated for malignant tumors.

Background: Our previous studies have shown that signal transducer and activator of transcription 3 (STAT3) signaling is important for the development of pancreatic microvasculature via its regulation of vascular endothelial growth factor-A (VEGF-A). Pancreas-specific STAT3-KO mice exhibit glucose intolerance and impaired insulin secretion in vivo, along with microvascular alterations in the pancreas. However, the specific role of STAT3 signaling in the regulation of pancreatic islet development and function is not entirely understood., Methodology/principal Findings: To investigate the role of STAT3 signaling in the formation and maintenance of pancreatic islets, we studied pancreas-specific STAT3-KO mice. Histological analysis showed that STAT3 deficiency affected pancreatic islet morphology. We found an increased proportion of small-sized islets and a reduced fraction of medium-sized islets, indicating abnormal islet development in STAT3-KO mice. Interestingly, the islet area relative to the whole pancreas area in transgenic and control mice was not significantly different. Immunohistochemical analysis on pancreatic cryosections revealed abnormalities in islet architecture in STAT3-KO mice: the pattern of peripheral distribution of glucagon-positive α-cells was altered. At the same time, islets belonging to different size categories isolated from STAT3-KO mice exhibited normal glucose-stimulated insulin secretion in perifusion experiments in vitro when compared to control mice., Conclusions: Our data demonstrate that STAT3 signaling in the pancreas is required for normal islet formation and/or maintenance. Altered islet size distribution in the KO mice does not result in an impaired islet secretory function in vitro. Therefore, our current study supports that the glucose intolerance and in vivo insulin secretion defect in pancreas-specific STAT3-KO mice is due to altered microvasculature in the pancreas, and not intrinsic beta-cell function.

By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen's (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR); 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans.

In order to assess the effectiveness of compression elastography of the thyroid gland as a method for differential diagnosis to studies conducted in the pre-operative period, there were involved 34 patients with a mean age 46.6 +/- 2.7 years. Elastography in the real time was characterized, according to the method of estimating, by a relatively high sensitivity (85.2-92.5%) and accuracy (70.6-79.4%), but low (30%) specificity. The specificity of the method, as it turned out, could be improved by taking into account the level of thyroid stimulating hormone (TSH) in the blood or body mass index (BMI) of the patients and, therefore, reducing the number of false-positive findings. Further improvement in the pre-operative diagnosis of malignant tumors of the thyroid gland and the formation of appropriate risk groups could be based on a combination of cytologic, hormonal, genetic and instrumental methods, including the so-called shear wave elastography.

Obesity and atherosclerosis-related diseases account for over one-third of deaths in the western world. Controlling these conditions remains a major challenge due to an incomplete understanding of the molecular pathways involved. Here, we show that Wip1 phosphatase, a known negative regulator of Atm-dependent signaling, plays a major role in controlling fat accumulation and atherosclerosis in mice; specifically, Wip1 deficiency prevents both conditions. In the course of atherosclerosis, deletion of Wip1 results in suppression of macrophage conversion into foam cells, thus preventing the formation of atherosclerotic plaques. This process appears to be independent of p53 but rely on a noncanonical Atm-mTOR signaling pathway and on selective autophagy in regulation of cholesterol efflux. We propose that the Wip1-dependent control of autophagy and cholesterol efflux may provide avenues for treating obesity and atherosclerosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Maintenance of glucose homeostasis depends on adequate amount and precise pattern of insulin secretion, which is determined by both beta-cell secretory processes and well-developed microvascular network within endocrine pancreas. The development of highly organized microvasculature and high degrees of capillary fenestrations in endocrine pancreas is greatly dependent on vascular endothelial growth factor-A (VEGF-A) from islet cells. However, it is unclear how VEGF-A production is regulated in endocrine pancreas. To understand whether signal transducer and activator of transcription (STAT)-3 is involved in VEGF-A regulation and subsequent islet and microvascular network development, we generated a mouse line carrying pancreas-specific deletion of STAT3 (p-KO) and performed physiological analyses both in vivo and using isolated islets, including glucose and insulin tolerance tests, and insulin secretion measurements. We also studied microvascular network and islet development by using immunohistochemical methods. The p-KO mice exhibited glucose intolerance and impaired insulin secretion in vivo but normal insulin secretion in isolated islets. Microvascular density in the pancreas was reduced in p-KO mice, along with decreased expression of VEGF-A, but not other vasotropic factors in islets in the absence of pancreatic STAT3 signaling. Together, our study suggests that pancreatic STAT3 signaling is required for the normal development and maintenance of endocrine pancreas and islet microvascular network, possibly through its regulation of VEGF-A.

Color Doppler mapping (CDM) of the regional lymph nodes was performed in 152 patients with primary skin melanoma without clinically determined regional and distant metastases. The patients were divided into 2 groups. The first group included 52 patients in whom biopsy was fulfilled after sonography and CDM of the regional lymph nodes. The second group (control) included 100 patients. After sonography and CDM biopsy of the lymph nodes was not fulfilled. Using CDM of the regional lymph nodes in the preoperative period allowed unjustified lymphadenectomies in patients with skin melanoma to be avoided. An algorithm of preoperative diagnosis of the degree of regional spreading of skin melanoma was developed which will give better results of treatment. The method of color Doppler mapping was first used for the detection of micrometastases of the tumor in the regional lymph system.

Vertebrates express at least 15 different synaptotagmins with the same domain structure but diverse localizations and tissue distributions. Synaptotagmin-1,-2, and -9 act as calcium sensors for the fast phrase of neurotransmitter release, and synaptotagmin-12 acts as a calcium-independent modulator of release. The exact functions of the remaining 11 synaptotagmins, however, have not been established. By analogy to the role of synaptotagmin-1, -2, and -9 in neurotransmission, these other synaptotagmins may serve as Ca(2+) transducers regulating other Ca(2+)-dependent membrane processes, such as insulin secretion in pancreatic beta-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic beta-cells. To determine whether synaptotagmin-7 regulates Ca(2+)-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor controlling insulin secretion in pancreatic beta cells.

Diagnostic procedures for skin melanoma in regional lymph nodes were compared in 250 patients. Doppler effect examination and sentinel biopsy were carried out in 60 patients with primary skin melanoma and clinically intact lymph nodes. Identical examination and regional lymphadenectomy were used in 80 patients with clinically detectable metastases to regional lymph nodes. The same procedures were performed in 110 healthy controls. Histological findings fully confirmed Doppler effect evidence. Regional lymphadenectomy was indicated only in patients with verified Doppler effect-related metastatic lesions to the lymph nodes.

Pulmonary and pleural involvement was identified in 17% (42.2% at the debut of the disease, while 57.8%--in the course of tumor progression) out of 264 children with Hodgkin's disease. Basing on X-ray evidence, pulmonary lesions were classified as perinodal, focal-infiltrative, disseminated, nodular, mixed infiltration and lobitis, while those of the pleura--exudative pleurisy and tumor masses involving the pleura. Focal-infiltrative pattern was most common (53%). The best results were reported in the treatment of perinodal infiltration, whereas the worst--disseminated and mixed infiltration as well as pleural lesions.

Ultrasound examination was carried out in 252 patients following specific treatment of uterine and ovarian malignancies. To compare the effectiveness of diagnostic procedures, transabdominal and transvaginal examinations were performed in succession in all the patients using ultrasound (Doppler) technique. Transvaginal study proved relatively more sensitive (98.9%) and diagnostically accurate (97.2%) in detecting relapse. Transabdominal examination carried out in conjunction with color Doppler imaging was best for metastasis detection.

Application of a modern method of introscopy--electroimpedance tomography (EIT) for diagnosis of different types of lung diseases is described. The EIT system including measurement and collecting data devices, 16-electrodes array and IBM PC 486 computer was used. The results of analysis of electrotomograms have demonstrated that the EIT-system can be introduced for detecting abnormal lung fluid levels, pulmonary edema, diagnosis of lung cancer, emphysema, pleuritis, hydrothorax, sarcoidosis. The method provides high sensitivity to the changes in the body physiological state. Other advantages are: safety, fast measurements, ease of equipment transportation and maintenance, low cost.

The paper deals with the use of the present-day highly effective method of introscopy electric impedance tomography (EIT) for diagnosis latent abnormalities during mass screening. EIT images viscera and tissues on the basis of their electric conductivity differences. Reconstruction of the images reflecting the distribution of electric conductivity values in the body is made from the recording potentials onto the body's surface while passing currents through the electrodes located along the circumference of the body's part under study. The 16-electrode EIT system developed by Dipol (Moscow) was used to examine the distribution of electric conductivity values in the extremities and chest organs in healthy volunteers of both sexes and in patients with various pulmonary diseases.

Inner diameter, absolute and relative wall thickness, and blood flow velocity in arterioles of different branching orders were measured in the rat skeletal (cremaster) muscle. It was found that as the branching order increased the heterogeneity of arterioles with respect to their relative wall thickness also grew. In response to papaverine-induced relaxation of the smooth muscle, there was a direct correlation between vasodilatation and the relative wall thickness. It was shown that a degree of smooth muscle shortening in different arterioles varied widely, the relative wall thickness being a measure (characteristic) of this shortening.

Action of the synthetic substance P (SP1-11) and its modified fragment (MSP1-4) on microhemodynamics was investigated in experiments. Significant hypotensive effect and reduction of blood flow velocity in rat mesenteric microvessels were produced by both substances, no changes of microvessels diameter were observed. Effective concentrations of the SP1-11 and MSP1-4 were revealed, being 10(-6) M and 10(-4) M, respectively. Organ specificity of substance P vascular effects is suggested.

Equations reflecting relationships between the thickness of blood vessel wall (w) and internal radius (r) of the vessel during the process of smooth muscle fiber contraction involved two types of the fibers orientation in vessel wall: at an angle of 45 degrees and 90 degrees to the longitudinal axis of the vessel. Experimental values of w and r were determined on arterioles of the rat mesentery after vasopressin or epinephrine administration. According to the degree of longitudinal and transversal efforts participation in the process of vessel closure, heterogeneity of the arterioles was revealed by comparison of the theoretical and experimental values of w and r. The ability of arterioles for closure did not depend on the initial value of relative vessel wall thickness (w/r).

Blood flow velocities in microvessels of the rat intestinal mesentery were determined by means of prism-grating method. Mean velocity values in arterioles were 1.9 +/- 0.1, in venules 1.2 +/- 0.2, in capillaries 0.82 +/- 0.06 and in arteriole-venule anastomoses 1.7 +/- 0.2 mm/s. These values do not vary significantly in arterioles with internal diameter from 23.2 to 6.9 mm and in venules from 7.2 to 28.2 mm. The most significant velocity changes appear in the passage of arterioles into capillaries (50%) and between capillaries and venules (40%).