Analysis of several BRCA1 and BRCA2 mutations in a hospital-based series of unselected breast cancer cases.

BACKGROUND: The distribution of BRCA mutations varies significantly between populations. The spectrum of BRCA1 and BRCA2 mutations in breast cancers in the Romanian population is incompletely known. The aim of the present study is to investigate the presence of nine BRCA mutations in patients with breast cancer identified in a surgical clinic from Bucharest. METHODS: Unrelated women diagnosed with breast cancer from Coltea Hospital (n=114) and healthy controls (n = 150) were selected for this study. Seven mutations in BRCA1 (185delAG, 5382insC, 943ins10, E1250X, 1294del40, E1373X, R1443X) and two in BRCA2 (IVS16-2A4G and 6174delT) were tested using PCR based protocols. In addition, the presence of BRCA1 185delAG, BRCA1 5382insC, BRCA2 6174delT mutations were tested with a post amplification mutation detection system, based on the ELISA method. RESULTS: Two patients with sporadic breast cancer (2%) and one patient with family history of the disease (7.14%) have the BRCA1 5382insC mutation. No other mutation was detected in patient and control groups. The mutations were not present in the control lot. CONCLUSIONS: Our results indicate that BRCA1 5382insC is a common mutation in Romanian women with breast cancer (3 114).

Morphological and immunohistochemical criteria of tissue response to radiotherapy in rectal cancer.

AIM: Given the context that rectal tumours respond to a certain degree to radiotherapy, a necessity arises for estimating a tumour's capacity to react to radiation from the very moment of diagnostic biopsy. MATERIAL AND METHODS: We have histologically and immunohistochemically analysed tissues coming from 52 patients with rectal adenocarcinomas. RESULTS: Of the studied parameters, the ones presenting significant variation under radiotherapy in terms of statistics(p 0.05) were: colloid type (p=0.001), EGFR in the tumour(p=0.00045), EGFR in the normal epithelium (p=0.0017),VEGF in the tumour (p=0.0132) and VEGF in the tumour stroma (p=0.030). CONCLUSIONS: Our study follows the same trends as the medical literature we have consulted regarding the variation of EGFR and VEGF with radiotherapy, and the distinct note of our study relies in the observation that normal stroma in case of rectal tumors also reacts to radiotherapy, sometimes more aggressively than the tumor itself, especially in which concerns the nerve and muscle fibers.

The lipid alterations in the stratum corneum of dogs with atopic dermatitis are alleviated by topical application of a sphingolipid-containing emulsion.

BACKGROUND: Atopic dermatitis (AD) results from an altered skin barrier associated with defects in the lipid composition of the skin. Dogs with AD present similar clinical symptoms to humans, and may be a useful model for investigations into AD. AIM: To analyse the changes occurring in the lipids of the stratum corneum (SC) of dogs with AE after 3 weeks of topical treatment with an emulsion containing ceramides, free fatty acids (FFAs) and cholesterol (skin lipid complex; SLC). METHODS: Nonlesional SC was collected by tape stripping from control and treated areas. Free and protein-bound lipids were purified, and the various classes were isolated by column chromatography, analysed by thin-layer chromatography and assayed. RESULTS: Ceramides, FFA and cholesterol were all found to be lower in the skin of untreated dogs with AD than in normal dogs, and the topical treatment resulted in significantly increased values for ceramides. Conversely, only trace amounts of glucosylceramides were present in normal SC, but a high concentration (27 µg per mg protein) was detected in canine atopic SC, which disappeared after treatment with SLC. There was a heterogeneous distribution of all of the lipids in the different layers of canine atopic SC, which was more pronounced for protein-bound than for free lipids. Following topical treatment, the protein-bound lipid content normalized. CONCLUSIONS: Topical treatment with SLC resulted in a significant improvement of the lipid biosynthesis of keratinocytes in atopic dogs, thereby potentially enabling the formation of a tighter epidermal barrier.

[Synchronous gastrointestinal stromal tumor (GIST) and multiple digestive neoplasms, benign and malignant]. / Tumora gastro-intestinala stromala (GIST) asociata sincron cu multiple neoplazii digestive benigne, precursoare si maligne.

Gastrointestinal stromal tumors (GIST) are a broad category of mesenchymal, non-epithelial primary tumors of the digestive tract, located in the wall of hollow viscera, from the esophagus to the anus and often in adjacent mesentery and omentum. They are clinically unpredictable (may be discovered incidentally during an imagistic investigation or during surgery for other pathological entity, or at necropsy) and also have an unpredictable behavior (GISTs with very low risk, with low or moderate malignancy, which have benign histopathologic features but can recurr or can metastasize). The case we present here represents a rare association between a synchronous gastrointestinal stromal tumor (GIST) and multiple gastric benign and malignant tumors.

Predictive ability of coronary computed tomography angiography parameters in patients suspected of obstructive coronary artery disease: a single-center cross-sectional study.

OBJECTIVE: Coronary computed tomography angiography (CCTA) is becoming increasingly useful for the diagnosis of coronary artery disease (CAD). Coronary calcium score (CCS), epicardial fat volume (EFV), and number of coronary plaques (NoP) add important information for the risk stratification and prognosis prediction of these patients. However, evidence about their ability to predict obstructive CAD is limited. We sought to evaluate the ability of CCTA parameters in predicting obstructive CAD. PATIENTS AND METHODS: We conducted a cross-sectional, single-center study on patients at risk to develop CAD. CAD was defined as coronary stenosis > 50% after the other one (CCS, EFV and NoP were determined by CCTA). CCS was then ranked 5 severity groups: 0, 1-99, 100-399,400-999, and ≥1000. NoPs were classified in four categories: no plaques, 1-5, 6-10 and ≥10. Logistic regression analyses were performed, and statistical analysis was considered significant if p<0.05. RESULTS: Of all 540 patients (55.8±11.1 years) who met the enrolment criteria, 98 had obstructive CAD. CCS, EFV and NoP were significantly associated with the presence of obstructive CAD (p<0.0001). The area under the receiver operating characteristics (ROC) analysis revealed significant cut-off values (p<0.0001) of CCS (70.3), EFV (40.8), NoP (4) for predicting obstructive CAD. Their association proved to have an AUC of 0.969, and a specificity of 95%. A scoring system based on regression coefficients which proved to have statistical significance for obstructive CAD as further constructed. It included EFV, CCS and left ventricular ejection fraction. This scoring system significantly predicted obstructive CAD for a cut-off value of 62.46, with a NPV of 96.3%. CONCLUSIONS: The combined use of CCS, EFV and NoPs increases the predictive ability for obstructive CAD of each parameter used alone. These could be useful for developing a novel scoring system.

The weak rate of sphingolipid biosynthesis shown by basal keratinocytes isolated from aged vs. young donors is fully rejuvenated after treatment with peptides of a potato hydrolysate.

A new study was carried out to bring more information on the effect of the potato proteins ferment. Basal keratinocytes obtained from freshly excised skin samples of two groups of five donors, a young one (25-36-year-old) and an aged one (59-70-year-old) were established in culture. The results showed a downward trend in the content of all lipid fractions in untreated keratinocytes of aged donors when compared with young ones. We found major differences in the response of keratinocytes to potato proteins ferment treatment between young and old donors. Whereas the lipid content of cells from young donors increased either moderately or actually decreased in some cases in comparison with the untreated controls, the lipid biosynthesis was strongly stimulated in aged donors' keratinocytes whose lipid contents globally became close to those found in young donors. However, the changes elicited by potato proteins ferment treatment were not seen at the same extent for all lipid classes. Cholesterol content increased up to three-fold and alpha-hydroxy fatty acids were augmented up to seven-fold, whereas the increase in normal fatty acids was quite moderate. In sphingolipids labelled by incubation of keratinocytes in culture medium containing [(14)C]-serine, ceramides and glucosylceramides in cells from aged donors showed the highest uptake of radioactivity, with somewhat less incorporation in sphingomyelin and gangliosides. Therefore, it seems that potato proteins ferment has a much more potent stimulatory activity on the lipid biosynthesis of basal keratinocytes of aged donors, thereby normalizing the cellular lipid content that obviously decreases along with ageing. Although our results were obtained only with basal keratinocytes in this study, potato proteins ferment could be beneficial to maintain an efficient skin barrier in ageing people, provided that the peptides can get through to the basal membrane upon topical application.

[Adenoid cystic carcinoma of the breast--two case reports]. / Carcinom adenoid chistic mamar--prezentare a doua cazuri.

Adenoid cystic carcinoma is a rare type of breast carcinoma with a good prognosis. It represents less than 0,1% of breast carcinomas. We present two cases of adenoid cystic carcinoma diagnosed in the Surgical Department of Coltea Hospital in the last 3 years. The first case is a 66 years old patient with a breast tumor that has clinical and imagistic features compatible with a benign diagnosis. The frozen sections established the diagnosis of adenoid cystic carcinoma, confirmed by histopathologic examination of paraffin embedded tissue and immunohistochemistry. The second case is a 68 years old patient with a breast tumor located in the central quadrant of the left breast, with skin infiltration. Preoperatory fine needle aspiration is sugestive of a papillary tumor, so the cytologic exam cannot establish malignancy. The frozen sections established the diagnosis of ductal invasive carcinoma and histopathologic examination of paraffin embedded tissue and immunohistochemistry established the diagnosis of adenoid cystic carcinoma associated with ductal invasive carcinoma grade I and adenomyoepitelioma. The cytology had a false papillary aspect, in fact there was amorphous material contained in pseudoluminal spaces. In both cases the treatment was surgical resection with tumor excision and free resection margins. In the second case lymphadenectomy was also performed.

MTRR polymorphism and the risk for colorectal and breast cancer in Romanian patients--a preliminary study.

BACKGROUND: The risk of colorectal cancer (CRC) and breast cancer (BC) is influenced by polymorphisms located in the genes encoding enzymes of the folate pathway. The aim of this study was to evaluate if A66G MTRR (rs1801394) polymorphism is involved in predisposition for colorectal and breast carcinogenesis in Romanian patients. MATERIALS AND METHODS: In the present case-control study, 300 individuals divide in four groups: sporadic CRC patients (n = 120), control CRC (n = 60), BC patients (n = 60) and control BC (n = 60), were genotyped by PCR-RFLP method. RESULTS: Frequency of genotype AA was 11.7% in CRC control and 5% respectively in BC control. For cancer groups the frequency of genotype AA was 9.2% in CRC and 0% in BC. CONCLUSIONS: Study results do not demonstrate an association between A66G MTRR polymorphism and CRC or BC in Romanian patients.

Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1.

Thrombospondin-1 (TSP1) has potent biological effects on vasculature smooth muscle cells (SMCs) and endothelial cells. The regulation of extracellular accumulation of TSP1 is mediated by a previously obscure process of endocytosis which leads to its lysosomal degradation. Since members of the low density lipoprotein receptor (LDLR) family have been found to mediate endocytosis which leads to degradation of a diverse array of ligands, we evaluated their possible role in the uptake and degradation of TSP1 by vascular SMCs, endothelial-cells and fibroblasts. 125I-TSP1 was found to be internalized and degraded lysosomally by all these cell types. Both the internalization and degradation of 125I-TSP1 could be inhibited by a specific antagonist of the LDLR family, the 39-kD receptor-associated protein (RAP). Antibodies to the LDLR-related protein (LRP) completely blocked the uptake and degradation of 125I-TSP1 in SMCs and fibroblasts but not endothelial cells. Solid-phase binding assays confirmed that LRP bound to TSP1 and that the interaction was of high affinity (Kd = 5 nM). Neither RAP nor LRP antibodies inhibited the binding of 125I-TSP1 to surfaces of SMCs. However, cell surface binding, as well as, endocytosis and degradation could be blocked by heparin or by pre-treatment of the cells with either heparitinase, chondroitinase or beta-D-xyloside. The data indicates that cell surface proteoglycans are involved in the LRP-mediated clearance of TSP1. A model for the clearance of TSP1 by these cells is that TSP1 bound to proteoglycans is presented to LRP for endocytosis. In endothelial cells, however, the internalization of TSP1 was not mediated by LRP but since RAP inhibited TSP1 uptake and degradation, we postulate that another member of the LDLR family is likely to be involved.

Toward stomatal-flux based forest protection against ozone: The MOTTLES approach.

European standards for the protection of forests from ozone (O3) are based on atmospheric exposure (AOT40) that is not always representative of O3 effects since it is not a proxy of gas uptake through stomata (stomatal flux). MOTTLES "MOnitoring ozone injury for seTTing new critical LEvelS" is a LIFE project aimed at establishing a permanent network of forest sites based on active O3 monitoring at remote areas at high and medium risk of O3 injury, in order to define new standards based on stomatal flux, i.e. PODY (Phytotoxic Ozone Dose above a threshold Y of uptake). Based on the first year of data collected at MOTTLES sites, we describe the MOTTLES monitoring station, together with protocols and metric calculation methods. AOT40 and PODY, computed with different methods, are then compared and correlated with forest-health indicators (radial growth, crown defoliation, visible foliar O3 injury). For the year 2017, the average AOT40 calculated according to the European Directive was even 5 times (on average 1.7 times) the European legislative standard for the protection of forests. When the metrics were calculated according to the European protocols (EU Directive 2008/50/EC or Modelling and Mapping Manual LTRAP Convention), the values were well correlated to those obtained on the basis of the real duration of the growing season (i.e. MOTTLES method) and were thus representative of the actual exposure/flux. AOT40 showed opposite direction relative to PODY. Visible foliar O3 injury appeared as the best forest-health indicator for O3 under field conditions and was more frequently detected at forest edge than inside the forest. The present work may help the set-up of further long-term forest monitoring sites dedicated to O3 assessment in forests, especially because flux-based assessments are recommended as part of monitoring air pollution impacts on ecosystems in the revised EU National Emissions Ceilings Directive.

Studies of compounds that enhance sphingolipid metabolism in human keratinocytes.

Several products are known to inhibit the biosynthesis of ceramides and glucosylceramides, but very few stimulate this process. We studied the influence of a hydrolysate of potato proteins (Lipidessence) in vitro on the sphingolipid metabolism of normal human epidermal keratinocytes. By measuring growth with the thymidine uptake assay, it was seen that Lipidessence, added in the culture medium up to an 8% concentration, did not change significantly the proliferation rate of keratinocytes, but beyond this concentration a progressive dose-dependent inhibition of growth was noticeable. Following incubation of cells with the product at 5% and 10% concentrations for 2 days, the lipids were extracted. The different lipid classes were separated by fractionation on columns of aminopropyl silica gel and analyzed by high-performance thin-layer chromatography. When keratinocytes were cultivated in the presence of Lipidessence, the biosynthesis of cholesterol, phosphatidylcholine, phosphatidylserine and gangliosides was stimulated, and a major increase was noticeable in the biosynthesis of free fatty acids, free ceramides, glucosylceramide and sphingomyelin. Radioactive [(14)C]-serine was used as a precursor of sphingoid bases to study sphingolipid biosynthesis. After migration of lipid fractions on thin-layer plates, autoradiography showed that free ceramides and glucosylceramide were labeled, thus suggesting that de novo biosynthesis was accounting for the increased cellular content in sphingolipids.

Subcellular distribution and metabolic fate of exogenous ceramides taken up by HL-60 cells.

Ceramides (Cer) are key intermediates in the metabolism of sphingomyelin and are also important second messengers. We report that natural long-chain ceramides added to the incubation medium in microgram amounts are internalized in HL-60 cells as well as the short-chain analogue C2-Cer and targeted to various subcellular compartments. No significant difference was detected in the ability of HL-60 cells to metabolize exogenous Cer containing a short (acetyl) versus long (palmitoyl or oleoyl) acyl chain. After a 2-h incubation time with [14C]-C16 ceramides, most of the cell-bound radioactivity was found in free ceramides. Sphingomyelin was the major metabolized sphingolipid containing labeled ceramides and only a small proportion of exogenous ceramides were converted to neutral glycolipids and gangliosides. Up to 20% of the exogenous ceramides taken up by the cells were recovered in mitochondria, mostly as authentic C16 ceramides and C16 sphingomyelin, along with a trace amount of labeled GM3 ganglioside. These results are consistent with the notion that exogenous natural ceramides enter cells, can be further metabolized in situ and partly targeted to mitochondria, which are known to be involved in the control of programmed cell death.

[Stromal tumor of Meckel's diverticulum--a rare source of gastrointestinal bleeding and a real diagnostic problem]. / Tumora stromala de diverticul Meckel--cauza rara de hemoragie digestiva si problema de diagnostic.

Although Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract, complications in adults are rare, especially in the elderly. Lower gastrointestinal bleeding as a result of Meckel's diverticulum with ectopic gastric mucosa is unusual among the elderly. The case we report involved a 69 year old man with gastrointestinal hemorrhage found to be due a stromal tumor developed on Meckel's diverticulum. We considered our case interesting because of its rarity and of preoperative diagnosis difficulty.

Occurrence of ceramides and neutral glycolipids with unusual long-chain base composition in purified rat liver mitochondria.

The free ceramide content of rat liver mitochondria was found to be 1.7 nmol/mg protein and outer membranes contained a three-fold higher concentration than inner membranes. The mitochondrial content in neutral glycolipids was 0.6 nmol/mg protein. The long-chain bases found in free ceramides were d18:1 sphingosine, d18:0 3-ketosphinganine and t21:1 phytosphingosine in increasing order. In contrast, 3-ketosphinganine was the only base of glucosylceramide and lactosylceramide of inner membranes, whereas d18:1 sphingosine was the major long-chain base of glucosylceramide of outer membranes.

A set of glycoproteins recognized by A2B5 antibody with major bands at 55 and 76 kDa is overexpressed in human head and neck squamous cell carcinomas.

A2B5 antibody was found to strongly label frozen sections of human head and neck squamous cell carcinomas. The low amount of glycolipids (c-series gangliosides and sulfatides) purified from the same tumors and reactive with A2B5 by immunostaining on thin-layer plates could not account for the high level of tissue labeling. Proteins were extracted from both normal tissues and squamous cell carcinomas and analyzed by Western blot with A2B5 antibody on PVDF membranes. The antibody was found to stain a set of glycoproteins with two major bands at 55 and 76 kDa present in normal tissues and overexpressed in carcinomas. Staining was abolished by prior treatment of the PVDF membranes either with Arthrobacter ureafaciens neuraminidase or with a solution of 10 mM periodate that is known to destroy carbohydrates. Our results show that the carbohydrate epitope recognized by A2B5 antibody can be displayed by both glycolipids and glycoproteins.

Clinical results of the Pop De Popa xenobioprosthesis in patients with advanced heart failure: long-term follow-up of 562 patients.

From January of 1984 through December of 1990, we implanted 739 Pop De Popa wild boar aortic valves in 626 patients, in all cardiac valvular positions. Of these patients, 562 received only the Pop De Popa xenobioprostheses, which numbered 620 valves. Only patients with contraindications for bioprosthetic valves (such as children under the age of 15) were excluded. At surgery, the 562 patients ranged in age from 17 to 66 years (mean, 41.7 yrs). Five hundred thirty-one (94.48%) were in NYHA functional class III or IV before valve replacement. Of the 620 valves implanted, 20 were replacements for Pop de Popa prostheses and the other 600 were replacements for native valves. Survivors were followed-up for a mean period of 31.6(+/-22) months (range, 3 months to 7 years), and for a cumulative period of 2,432 patient-years. Over the 7-year period of study, there were 78 late deaths, and 32 other patients were lost to follow-up. The analysis demonstrated good cardiac and general improvement. At the conclusion of the 7-year study, 94.83% of the survivors subject to follow-up were in NYHA functional class I or II. The early mortality rate was 12% (68 patients), and the following incidence of early valve-related complications was noted: thromboembolism, 3% to 4%; endocarditis, 1% to 2%; paravalvular leak, 1% to 2%; primary tissue failure, 1%; and anticoagulant-related hemorrhaging, 1%. At 7 years, 90% of survivors subject to follow-up were still free of valve failure. The probability of complications was as follows: thromboembolism, 16.1%; endocarditis, 8.8%; paravalvular leak, 4.4%; anticoagulant-related hemorrhaging, 1.2%; and valvular degeneration and reoperation, 12.5%. The probability of survival at 7 years was 86.12%. While this study does not yet demonstrate the superiority of the wild boar valve over other bioprosthetic valves, it does reaffirm the worth of implanting biologic valves in adult patients when not contraindicated. Perhaps as we continue follow-up beyond 7 years, the apparent durability of the wild boar cusps will manifest itself in a statistically significant manner.

Bioactive polymers. 70. The kinetics of controlled release of neomycin in an alkaline medium.

Neomycin is coupled on xanthan--a polysaccharide of microbial biosynthesis produced by Xanthomona campestris--through ionic complexation. The kinetics of neomycin release, in vitro, at pH = 8.2 is studied. A release of neomycin, following a zero order kinetics, is observed, regardless of the eluent flow-rate. The neomycin-xanthan complex, protected by a cellulosic membrane, behaves like a monolithic-type device. Diffusion coefficients--increasing with increasing the eluent flow-rate--are also calculated.

[Mental and behavior disorders in children placed in long term care institutions in Hunedoara, Cluj and Timis, Romania]. / Les troubles mentaux et les troubles du comportement des enfants placés en établissement de long séjour dans les judets de Hunedoara, Cluj et Timis, Roumanie.

This article originated from a descriptive study done in 1992-1993 in Romania. The study was initiated and coordinated by the French NGO "Médecins du Monde", was directed by three health organizations (the "Observatoire régional de la santé de Languedoc-Roussillon", the "Unité 265 INSERM", the Romanian League for Mental Health) and was granted by the Romanian government and the European Community Commission. There are many publications about children's mental and behavioural disorders. But there are few epidemiological studies concerning the prevalence of these disorders among children suffering from social difficulties. This article explores the prevalence of mental and behavioral disorders among Romanian children institutionalized and examines specifically the prevalence among children in homes for children ("Casa de Copii") to compare it with similar data published in other countries. First, this article explores the prevalence of mental and behavioral disorders among a population of 4.692 children institutionalized in three Romanian districts in 1992. Second, this article examines the prevalence of these disorders among a population of 1.610 children institutionalized in homes for children ("Casa de Copii"), i.e. 1,610 children ages ranging from 4 to 18 years and suffering from social difficulties. Homes for children are out of home care institutions which are specialised neither in physical deficiencies nor in mental disorders. From this population, a randomized sample of 508 children has been screened by physicians and psychologists based on an evaluation protocol. Then each disorder has been coded as a diagnosis, according to the Tenth International Disease Classification (WHO). Fifty-four percent (54%) of the children institutionalized in homes for children in three Romanian districts in 1992 had a main diagnosis of mental or behavioural disorder. Third, this article compares our results to the prevalence found in other studies. Only three studies could be selected for comparison because they were the only ones with the three following criteria: 1) a focus on a population of children or a randomized sample of children ages ranging from 4 to 18 years, 2) a focus on children suffering from social difficulties and living in out of home care, 3) disorders evaluated by health professionals or a validated methodology. Our results lies within the range of prevalence found in the literature (41-70%). A discussion follows regarding methodological matters and critiques that may be launched from such a comparative designs. Finally, the high frequency of institutionalization in Romania in 1992 illustrates how few solutions there were to social difficulties and how exaggerated institutionalization was. This was a very different situation compared to Western Europe and Northern America. This should not hide, however, the actual modifications that took place in Romania. This article concludes with a brief description of the modifications which have been generated by the evaluation protocol used here.

[Esophageal stenosis and esophagotracheal fistula with concomitant gastric ulcer in "caustic soda" ingestion]. / Stenoza de esofag si fistula esotraheala însotite de ulcer gastric, în ingestia de "soda caustica".

The article deals with a special case through it's gravity and lesional complexity. A forty years old ill person with esophagus stenosis and postcaustic esophagotracheal fistula, having both a gastric ulcer on the date of surgery is operated in three stages: 1. Vagotomy, pyloroplasty and gastrotomy. 2. Esophagectomy with Kirschner-Nakayama gastric grafting. Posterior tracheorraphy with esophageal muscular patch. 3. Anastomotic cervical stenosis--plastic replacement (grafting) with a fat-less skin.

Ultrastructure of the adipose tissue matrix in children with malnutrition.

Bioptic fragments of adipose white tissue taken from trochanterian area from children of 2-22 months old were ultrastructurally investigated. Children were of both sexes, 5 normal and 22 with clinical diagnosis of malnutrition. There were studied many interadipocyte spaces signalling out in cases with malnutrition modifications of different components, some of them related with the degree of malnutrition. There were noted: disorganisation and disappearance of basal membranes of capillaries and glycolema; modifications of endothelial cells with lesions of the capillary wall and free degraded red blood cells; disorganization of the ground substance in small areas or sometimes extended to all matrix of the space; collagen fibres reduced in number and size, and in two cases the presence of collagen fibrils with severe lesions, realeasing an electrondense material, fibrinoid-like; matrix infiltration, in some cases with lipids. In only one interadipocyte space a synaptic button was noted in contact with capillary. In malnutrition lesions of cellular elements of the white adipose tissue the following were observed: adipocytes, fibroblasts, fibrocytes, endothelial cells, mast cells--which in their turn are responsible for modifications of macromolecular structures of the extracellular matrix--glycosaminoglycans, proteoglycans, components of which biosyntheses are cell-dependent.