Extracellular fibrillar matrix architecture of human placental villi at term.

The spatial organisation of the extracellular fibrillar matrix of normal human placental villi at term can be directly visualised by scanning electron microscopy after 2N-NaOH maceration technique. By these methods, the extracellular fibrillar matrix of placental villi appears as a continuous network of isolated collagen fibrils and/or small fibrillar bundles interwoven each other. This sort of "collagenous fibrillar skeleton" forms the axis of chorionic villi and connects them with the basal plates running through the whole villous system of the placenta. Significant variations in the spatial arrangement as well as in the quantity of the extracellular matrix is observed at different levels of the villous ramification. Within the stem villi, the fibrillar extracellular matrix are abundant and, whereas the fibrils near the villous surface run parallel to the longitudinal axis of the villous (outer fibrils), those located in the inner core of the villous are arranged circularly around the wall of the fetal vessels (inner fibrils). In mature intermediate and terminal villi, viceversa, the extracellular fibrillar matrix is significandy reduced and the fibrils are mainly organised in a thin circular layer around the capillaries and sinusoids. The present study demonstrated the existence of a diverse spatial architecture of the extracellular matrix that results to be peculiar to the various levels of the ramification of the villous tree. Therefore, these morphological data strongly suggest a "compartmentalisation" of the villous tree as suggested by previous immunohistochemical study. Such a highly organised "collagenous fibrillar skeleton" stresses the important mechanical role of the extracellular matrix in sustaining the chorionic fetal vessels and the trophoblastic layer. Furthermore, the fine reticular-meshed network observed within the terminal villi suggests that at this level an additional role ensuring a favourable milieu for active feto-maternal exchanges may exist.

Application of low intensity laser radiation in extravasal infiltrates caused by cytostatics in children with acute leukemia.

Application of low intensity laser radiation in the field of infantile oncohematology has not been discussed in the available medical literature. The possible adverse effect of the physical factors on the main disease and the controversial character of their application prevent their being used in the treatment of these diseases. The aim of the present study was to assess the feasibility of using low intensity laser radiation (LILR) in treating extravasal infiltrates caused by cytostatics (vincristin, daunorubicin) administered in children with acute leukaemia (AL). We applied laser therapy in a group of children with AL in the stage of exacerbation. The children were undergoing chemotherapy with cytostatics. Immediately after formation of the extravasal infiltrates the constant leaders in the venous duct were removed and low intensity laser therapy with LMS "Prometheus" was administered. This apparatus is a semi-conducting soft laser in the infrared spectrum (890-910 nm wavelength, depth of penetration 25-30 mm) working in an impulse mode. We used minimal doses in the range of the anti-inflammatory enthrophic frequencies. We found that the extravasal infiltrates rapidly decreased the local inflammatory response and the pain was relieved. The strong anti-inflammatory effect can be accounted for by the nonspecific action of the LIRR on the tissues, which is manifested by better microcirculation, removal of toxic substances and stimulated regeneration capabilities of the cells. This study is an attempt to work successfully in this very delicate field of the contemporary medicine despite the abstention from using it before.

Prognostic significance of the immunological variant in patients with multiple myeloma.

INTRODUCTION: The prognostic significance of the immunological variant and especially of the type of light chain secretion in multiple myeloma is controversially assessed in the literature. OBJECTIVE: To study the prognostic significance of the class and type of the monoclonal production in patients with multiple myeloma. PATIENTS AND METHODS: 109 patients with multiple myeloma were enrolled, in the study, diagnosed and treated at the University Clinic. The class and type of the paraprotein secretion was determined using immune electrophoresis of serum and/or urine by Grabar and Williams, Mancini radial immunodiffusion and Ouchterlony immunodiffusion for light chain typing. The median survival (MS) was calculated using the method of maximal logarithmic authenticity, where the survival in months = log t. RESULTS: The MS of all patients was 29 months. Patients with Bence Jones myelomas showed the lowest survival--12 months; followed by those with IgD myelomas--20 months. The patients with combined and non-combined light chain production (BJ+) lived 26 months, with BJ(-)--35 months (inauthentic difference). No difference was found between the survival of BJ(kappa)--30 months and BJ(lambda)--21 months. BJ(+) patients with myeloma nephropathy and nitrogen retention had a MS of 23 and 20 months, respectively, as compared with the BJ(+) patients without myeloma nephropathy and nitrogen retention: 47 and 40 months (p < 0.05). DISCUSSION AND CONCLUSION: The class of the paraprotein secretion only and the two types of light chain separately do not possess any prognostic significance. From a quantitative point of view the class and type of paraprotein production are independent staging criteria with certain predictive value. The prognostic significance of BJ-proteinuria is found making comparison between the groups in which its pathogenic effect is expressed.

The extracellular matrix of normal human placental villi at term: a scanning electron microscopy study.

The three-dimensional organisation of the extracellular fibrillar matrix in normal human placental villi at term is investigated by scanning electron microscopic after 2N-NaOH-maceration technique. The latter method consists of a chemical digestion of cellular components of the villi that allows the visualisation of the extracellular fibrillar network in a real three-dimensional fashion by scanning electron microscope. By this approach, the extracellular fibrillar matrix, mainly composed by collagen fibrils, forms a continuous skeleton within the whole villous system of the placenta. This sort of collagenous fibrillar skeleton forms the axis of chorionic villi and connects them with the basal plates. Significant differences in quantity and arrangement of the extracellular matrix are observed at the various levels of the villous ramification. In fact, in the stem villi, the fibrillar extracellular matrix is considerable and the fibres are arranged longitudinally at the villous surface (outer fibrils) and circularly in the inner core of the villous around the wall of the fetal vessels (inner fibrils). On the contrary, in mature intermediate and terminal vili, the extracellular fibrillar matrix is significantly reduced and the fibrils are mainly arranged in a thin circular layer around the capillaries and sinusoids. The present study confirms morphologically the existence of a diverse organization of the extracellular matrix specific for the various levels of the villous ramification as suggested by previous immunohistochemical studies. Moreover, the presence of a highly organized collagenous fibrillar skeleton as observed in our study, stress the important mechanical role of the extracellular matrix in sustaining the chorionic fetal vessels and the trophoblastic layer. Furthermore, the fine reticular-meshed network of this skeleton observed in the terminal villi suggests an additional role of the extracellular matrix to ensure a favorable milieu for active feto-maternal exchanges at this level of the villous tree.

A study on the influence of basic nutrients on glucose and glycine transport in the small intestine.

INTRODUCTION: The present study addresses the questions of the onset of adaptation of the small intestine transport functions to different nutritional effects and of the extent to which the detected changes could be interpreted as adaptive. MATERIAL AND METHODS: Two independent experiments with male white rats as experimental animals were carried out. In the first experiment three groups of animals were subjected to a single administration of respectively unadulterated protein, carbohydrates and fatty food and were examined 4 hours after end of feeding. In the second experiment the same diets were applied in the course of 10 days. In both experiments the glucose and glycine absorption was studied by means of the method of accumulating preparation from the mucosa of small intestine "in vitro". RESULTS: We found that rapid readjustment responses to the nutritional effects of basic nutrients could be detected as early as 4 hours after the food intake only in the carbohydrate transport systems. In the case of amino acids adequate changes in their transport systems were registered as late as 10 days after their reception. CONCLUSIONS: The mechanisms of the rapid adaptive responses are probably not associated with any quantitative changes in the enzyme and transport capacity of the small intestine but amount to its efficient readjustment in accordance with the specific nutritional effect.

Prognostic assessment of the Durie and Salmon staging system in patients with multiple myeloma.

In a prospective study, covering a 10-year period, 109 patients with multiple myeloma (56 men and 53 women of mean age of 62) were followed. The patients were grouped according to the staging system of Durie & Salmon. They were treated uniformally with monochemotherapy with Cyclophosphamid, Melphalan and Glicocorticosteroids. The median survival for the different clinical stages was: I--53 months, II--31 and III--24 months. Significant difference between stages II and III with 98 patients (89.9%), was not found. Authentically, patients in II A compared to II B clinical stage had higher median survival of 40 and 26 months, respectively. So was IIIA compared to IIIB--38 and 18 months. It was found that the prognosis for the life expectancy of the patients depended to a greater degree on the extent of the renal function impairment at the time of diagnosis of the process, e.g., on the A and B substage (serum creatinin level > 160 mmol/l) than on the size of the tumour mass, respectively the clinical stage according to Durie & Salmon system.

Effect of food products on endogenous generation of N-nitrosamines in rats.

An experiment was conducted to study the efficacy of two tomato pastes and aronia nectar (fruit juice + pulp from the black chokeberry, Aronia melanocarpa Elliot) as inhibitors of nitrosamine production in cancer prophylaxis programmes. White male rats of the Wistar strain were employed in an acute trial. Aminopyrin+sodium nitrite (APSN) were used as precursors for generation of endogenous nitrosamine. The animals were allocated to different dietary groups and fed by intubation with APSN or APSN + food products. Introduction of tomato paste (TP), high-beta-carotene tomato paste (HCTP) and aronia nectar (AN) as inhibitors of N-nitrosamine formation exerted a positive effect on blood and liver variables which was demonstrated by decreased concentrations of glutamic-oxaloacetic transaminase (EC 2.6.1.1), glutamic-pyruvic transaminase (EC 2.6.1.2) and uric acid in serum and lipid content in hepatocytes. Animals treated with APSN developed dystrophic changes in liver such as centrolobular necrosis, intense exangia, and enlarged cells with two, often large, pyknotic nuclei, while the structure of livers of rats fed with TP, HCTP or AN was well protected and almost normal. TP had a particularly beneficial effect on serum total protein and albumin concentrations as had AN on the urea value. The inhibitory effect of the food products used is explained by their chemical nature including pH, ascorbic index (ascorbate:nitrate), lycopene and beta-carotene contents.

Collagen fibrillar skeleton in pregnant rabbit endometrium at term: a SEM study after NaOH maceration.

This paper describes the spatial organization of the collagen fibrillar skeleton in pregnant rabbit endometrium at term, employing an alkali/low temperature/maceration technique followed by scanning electron microscopic (SEM) observations. Parallel light microscopic (LM) and transmission electron microscopic (TEM) investigations were made to identify the location and possible changes in the endometrial collagen network. Two different types of NaOH maceration were applied, demonstrating separately: 1) the collagen structures (2N-NaOH maceration removes the cells and basal laminae); and 2) the cellular elements (6N-NaOH maceration removes the collagen fibrils). After 2N-NaOH maceration, the collagen network of the endometrium is seen in a superficial compartment around the glands and a deep compartment situated near the endometrial-myometrial junction. Significant changes are observed only in the superficial compartment. The luminal mucosal surface is characterized by numerous thin projections reducing the uterine cavity which, as a consequence, further appears very irregular and highly convoluted. The subepithelial collagen network is composed of densely packed fibrils with a woven course. It contains many tubular or channel-like invaginations (100-150 microns in width and 200-300 microns in length) where endometrial glands are located. These invaginations, corresponding to the glandular impressions, are extremely dilated, enlarged and variable in shape. The collagen fibrils are arranged concentrically around the glandular orifices without forming bundles. At the bottom of the spaces between the mucosal projections, small fenestrations (4-8 microns in diameter each) are present. They form small groups of about 10-20 in number and are due to the endometrial blood capillaries. The deep compartment of the endometrial collagen network is little altered, preserving its general lamellar arrangement. The changes in the endometrial collagen skeleton are due to a variety of complex mechanical and hormonal stimuli affecting the uterus during pregnancy. These may be significant for correct implantation, placentation and delivery.

The collagen skeleton of the human umbilical cord at term. A scanning electron microscopy study after 2N-NaOH maceration.

The organization of the collagen fibrils in the human umbilical cord at term is directly visualized by means of a scanning electron microscopy cell maceration method. This technique clearly reveals that there is a much more extensive collagen fibrillar architecture within the umbilical cord than that reported in the classical histological descriptions. The Wharton's jelly, in fact, appears as a spongy network of interlacing collagen fibres and small woven bundles apparently arranged at random and forming a continuous soft skeleton that encases the umbilical vessels. The collagen fibrillar network shows the presence of a wide system of interconnected cavities consisting of canalicular-like structures as well as cavernous and perivascular spaces. This system of cavities might play a mechanical role allowing the storing of the ground substance of the jelly and its diffusion during twisting or compression. Furthermore, it may have an important role facilitating the diffusion throughout the jelly of diffused materials (i.e. water and trophic metabolites) either from or to the umbilical vessels and the amniotic cavity, thus overcoming the lace of a proper vasculature with the jelly.

The collagen fibrils arrangement in the Wharton's jelly of full-term human umbilical cord.

In the present study, a cell maceration/scanning electron microscopy method is employed in order to reveal the three-dimensional organization of the collagen fibrils in the Wharton's jelly of the human umbilical cord at term. By this method the jelly appears as a three-dimensional network of collagen fibrils that runs continuously from the amniotic membrane to the umbilical vessels. A diverse architecture of the collagen fibrillar network in the inner and outer region of the cord is observed suggesting an anatomical as well as a functional compartmentalization. In fact, the network is soft in the inner part and it is characterized by canalicular structures whereas in the outer region the collagen is dense and the network is characteristically composed by a sponge-like system of cavernous spaces. It is suggested that these cavities might store the ground substance and allow its diffusion during twisting or compression of the cord. Furthermore they may facilitate the flow of metabolites throughout the jelly from and to the umbilical vessels and the amniotic cavity.

Collagen fibrillar network in estrous and hCG-stimulated rabbit uterus: a SEM study after NaOH maceration.

The three-dimensional (3-D) organization of the collagen fibrillar network in rabbit uterus was studied by cell maceration/scanning electron microscopy (SEM) method, both during estrus and after stimulation with 100 I. U. of human chorionic gonadotropin (hCG). The cellular elements of glutaraldehyde-fixed tissue were effectively removed with 2N-NaOH at 25 degrees C for 5-7 days, followed by rinsing in distilled water. Correlative light microscopy (LM) and transmission electron microscopy (TEM) observations were also made in order to better clarify the natural location and distribution of collagen structures in the uterine layers. In estrous and ovulatory rabbits the superficial compartment of the endometrial stroma was composed of diffusely organized individual collagen fibrils and thin bundles of fibrils, forming specific supporting structures around the uterine glands. The deeper stroma showed a more condensed lamellar arrangement, particularly in the central part of the endometrial folds (plicae). Two distinct collagen networks, detected in the circular and longitudinal muscle layers of the myometrium, represented plexuses of anastomosing fine sheaths around the individual smooth muscle cells. A condensation of the fibrillar framework was observed around the large blood vessels between these two layers. Little alteration in uterine fibrillar network could be noticed in ovulatory animals 12 h after stimulation with hCG. Marked changes indicating collagen reorganization occurred in progestational animals 7.5 days after hCG administration. In this case, the collagen fibrillar network of the endometrium showed an irregular pattern consisting of slender elongations surrounding the labyrinthine spaces of the epithelium and corresponding to numerous, extremely attenuated plicae. Such a rearrangement of fibrils is very likely a response to hormonal stimulation of the uterus. To further identify the location of the blood vessels in the uterine collagen skeleton, vascular casts were also prepared. The collagen fibrillar network not only provides a mechanical support for the structural components of the uterus but also creates a favourable milieu for their activities.

Ciliated fibroblasts and smooth muscle cells in the rat uterus.

Ciliation in endometrial fibroblasts and myometrial muscle cells of the rat was examined by transmission electron microscopy. Quantification of the number of ciliated cells during the estrus cycle did not show any firm relationship between ciliation and ovarian hormonal activity. In the case of most cilia, there is a spatial relationship between their basal centrioles and the Golgi complex, so that a Golgi-cilium complex is created. A possible role of ciliation in uterine fibroblasts and smooth muscle cells is discussed.

[Effects of physical activity and mid-alpine climatotherapy on serum lipids on adult diabetics and in obesity]. / Efekti na fizicheskata aktivnost i srednoplaninskoto klimatolechenie vurkhu serumnite lipidi u bolni diabet na zrialata vuzrast i zatlustiavane.

Observations and investigations were carried out on 50 patients with diabetes of mature years and light obesity of nutritional-metabolic type in a moderately high mountain (1870 m above sea level). After 20-day treatment, including daily, lasting physical loadings, cool sun-air exposures and moderately reducing diet of 1600-1800 kcal, a clinically significant reduction of a wide range 6,699-7,537 MJ = of lipid indices was established, namely--total fats, total cholesterol, beta lipoproteins, triglycerides, esterified fatty acids and lipoproteins with low density (LDL-cholesterol), an average with 9.3 to 19.5 per cent. A more pronounced reduction of lipid indices was established with higher initial values and moderate weight reduction with 3.5 kg for a 20-day treatment course. The physical loadings and cool sun-air exposure stimulated the lipolysis, the elevated levels of free fatty acids being chiefly used for energy supply of organism. The enhanced lipolysis was, very, likely, of essential significance for the favourable effect of hyperlipidemia.

[Effects of physical work on the glycemia, immunoreactive insulin and growth hormone in adult-onset diabetes]. / Efekti na fizicheskata rabota vurkhu glikemiiata, imunoreaktivniia insulin i rastezhniia khormon pri bolni s diabet na zrialata vuzrast.

Experimental observations were carried out upon 56 patients with diabetes mellitus at a mature age, with body overweight, compensation or a light metabolic decompensation. During physical work (approximately of 60 wt, in the form of hiking) a significant diminution of blood sugar was found during longer work -- 150 minutes. The better utilization of glucose is not associated with the changes in the immune reactive insulin level (IRI). Most likely a redistribution of IRI in the muscles occurs whereas phenomena of lipolysis develop in the adipose tissue. During physical work of 150 minutes in the form of hiking or 45 minutes veloergometric loading of 60 wt, a significant elevation of growth hormone (GH) was established, with a hypoglycemic effect and lipolysis in more than 50 per cent of the patients. Lipolysis has a more complicated mechanism and GH cannot be admitted to be the only factor, stimulating lipolysis.

[Changes in the indices of fat metabolism in obesity during physical activity, on a reducing diet and during meterological influences]. / Promeni v pokazatelite na mastniia metaolizum u bolni sus zatlustiavane pri fizicheska aktivnost, redutsirashta dieta i meterologichni vuzdeistviia.

Clinical experimental investigations were carried out of 96 patients with light, nutritional-metabolism forms of obesity under the conditions of a moderately high mountain (1870 m above the sea level). After a treatment course of 20--25 days including: reducing diet, physical loading and cool sun-air exposure, a significant decrease of a wide spectrum of lipid indices was found, namely: total lipids, triglycerides, total cholesterol, phospholipids and beta-lipoproteins. A significant correlation was established between cholesterol decrease and beta-lipoproteins with body weight reduction over 3 kg and the high initial values of the indices. With a single physical loading in the patients with obesity -- the elevation of NEFA does not considerably differ from that of the control group with neurasthenia. The glucose loading is admitted not to indice manifested lipogenesis with the physical loading and cool sun-air exposure.

[Effect of climatic exposure and physical activity on plasma cortisol levels and urinary 17-hydroxycorticosteroid excretion in patients with hypertension]. / Vliianie na klimatichni vuzdeistviia i fizicheska deinost vurkhu nivoto na plazmeniia kortizol i ekskretsiiata na 17-khidroksikortikosteroidi v urina pri bolni s khipertonichna bolest

Decrease in arterial pressure, mainly manifested in the first 5-10 days, was established in 111 patients with hypertension disease in functional and initial organic stage in the conditions of moderately high mountain (1870 m above sea level) after 25/20 days of complex climatic treatment including: active motor regimen, sun-air exposure and Pevzner diet No 10. Simultaneously the excretion of 17-hydroxicorticosteroids was increased in daily urine. Suprarenal cortex stimulation is best manifested after the first week and is kept till the end of the treatment. Cortisol plasma level was elevated in 42.7 per cent of the patients with hypertension disease with initial values under 15 mkg/100 ml plasma after three hours moderately severe physical activity, carried out in physiological thermal conditions and was decreased with 25.9 per cent with initial levels over 20 mkg/100 ml plasma. Parallely, 17-hydroxicoricosteroids secretion in urine was decreased as well as the systolic and diastolic arterial pressure.

[Study of the interrelationship of glycemia-nonesterified fatty acids in physical activity in diabetics and patients with a normal glucose tolerance test]. / Prouchvaniia vurkhu vzaimootnoshenieto glikemiia-neesterifitsirani mastni kiselini pri fizicheska aktivnost u diabetitsi i bolni s normalen gliukozotoleransen test

Sixty four experiments were carried out in middle aged diabetics with normal and over-normal body weight and in a control group of patients with NGTT with a parallel follow-up of blood sugar and NEFA with an uptake of 50 g glucose per os and the performance of a moderately difficult physical loading (hiking) or complete rest in a bed for 2.5 hours. A better glucose utilization was found after physical loading in both groups of patients as compared with the rest period. Glucose utilization in patients with diabetes mellitus in physical loading is the same independently of the blood sugar initial level, providing grounds to admit that the betacyte formation apparatus is not strained. NEFA decrease by the 60th minute in diabetics, both in physical loading and at rest does not substantially differ from the subject with NGTT. That comes to show that NEFA utilization in that period is almost the same for the two groups. In patients with NGTT at the end of the physicalloading NEFA is sharply elevated over the initial level (lipolysis), while in diabetics, they remained at the level of the 60th minute.