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The role of stable hydrogen isotopes in the thermoregulation and its regulation is poorly studied. We analyzed fluctuations in body temperature and changes in thermoregulation parameters in mice under conditions of reduced deuterium intake. The study was performed on male C57BL/6 mice that consumed water with a low (10 ppm) and normal (146 ppm) deuterium content. In 7 days, fluctuations of body temperature, locomotor activity, and oxygen uptake were assessed. Deuterium depletion in the body reduced the mean value of minute fluctuations of body temperature and the mean spectral density of minute fluctuations in body temperature in the 2-20-min periods. This attested to a stabilizing effect of deuterium depletion on the rhythms of body temperature fluctuations, without significant shifts in the thermogenesis parameters. Thus, drinking water with reduced deuterium content makes them less sensitive to external influences.

Dinitrosyl iron complexes with glutathione ligands (GS-DNICs) are a physiological form of nitric oxide that is stored and transported in the organism. In addition, these complexes can act as antioxidants and antiradical agents. It was shown that GS-DNICs protect hemoglobin (Hb) from oxidative modification by peroxynitrite. They prevent the formation of carbonyl Hb derivatives, the oxidation of tryptophan and tyrosine residues, degradation of the heme group, and the formation of interprotein cross-links. These complexes also inhibit the oxidation of dihydrorhodamine by peroxynitrite, which forms via the decomposition of 3-morpholinosyndonimine. In some cases, the antioxidant effect of GS-DNICs is comparable to that of reduced glutathione. The results allow GS-DNICs to be considered peroxynitrite interceptors and Hb protectors.

The study examined transcriptional regulation of adrenal zona reticularis development in male Wistar rats exposed to low doses of endocrine disruptor dichlorodiphenyltrichloroethane (DDT) prenatally and postnatally. At pubertal age, zona reticularis demonstrated a retarded growth with a low proliferative activity of its cells. At this age, zona reticularis was characterized with overexpression of β-catenin by steroid-producing cells; a high percentage of cells with membrane and cytoplasmic localization of β-catenin, and reduced number of cells with nuclear β-catenin attesting to insufficient activation of Wnt signaling. Expression of transcriptional factor Oct4 by reticularis cells was down-regulated indicating their diminished proliferative potency. No significant alterations in Sonic Hedgehog expression were observed. Thus, DDT-provoked disorders of transcriptional regulation result in abnormal development of zona reticularis thereby disturbing sexual maturation in males.

Skin represents a natural barrier and a site of contact with antigens. Skin demonstrates higher intensity of immune reactions compared to other organs, which implies the additional cell interactions. Dendritic cells are traditionally considered as the main antigen­presenting cells of the skin, however, in recent years, some data on the ability of another population, mast cells, to perform antigen­presenting functions have appeared. The review presents novel data on the interaction of skin dendritic and mast cells, including formation of immune synapses, exchange of surface molecules, and transfer of secretory material. The authors have developed and presented a new concept for the initiation and modulation of immune responses provided by the functional dendritic cell–mast cell complex. Keywords: dendritic cells, mast cells, skin, immunological synapse, degranulatory synapse, immune response

The study is aimed at elucidation of ultrastructural mechanisms underlying impaired aldosterone synthesis by glomerulosa cells in Wistar rats exposed to low doses of endocrine disrupter DDT during prenatal and postnatal development. Analysis of rat zona glomerulosa histology and function during the pubertal and postpubertal periods showed that exposure to endocrine disrupter DDT disturbs its development and reduced the production of aldosterone. Electron microscopy showed that changes in the aldosterone synthesis are related to impaired reorganization of the mitochondrial apparatus, one of the leading factors in the regulation of steroidogenesis, in glomerulosa cells in DDT-exposed rats during puberty.

Spontaneous proliferative activity of splenocytes in female CBA mice and the response of these cells to antigens of allogeneic male BALB/c and DBA/2 mice in a mixed splenocyte culture were evaluated by 3H-thymidine incorporation in different pregnancy models. ♀CBA×♂BALB/c mating was used for modeling physiological pregnancy. Spontaneous abortions were reproduced by abortion-prone ♀CBA×♂DBA/2 mating. In order to simulate immunostimulant-induced and immunostimulant-potentiated abortions, 0.83 mg/kg muramyl dipeptide β-heptylglycoside was intraperitoneally injected to CBA females mated with BALB/c or DBA/2 males, respectively, on gestation days 5 and 7. The increase in the rate of embryo resorption in the models of spontaneous, induced, and potentiated abortions occurred against the background of an increase in the level of spontaneous proliferation of splenocytes and a decrease in their reactivity to paternal antigens on gestation day 9.

Mast cells are active participants of innate immune response. Systemic immune response induces functional changes even in organs, which are not considered primary targets of bacterial or viral infections. Cytophysiology of mast cells located in organs not affected by systemic inflammatory response, like skin, is still poorly studied. Investiga- tions of this issue might elucidate some pathogenetic mechanism of skin diseases associated with previously devel- oped intestinal or respiratory infection. The aim was to investigate structural changes of rat skin mast cells in systemic inflammatory response indicative of mast cell secretion. Materials and methods: The experiment was performed on 45 male Wistar rats. Systemic inflammatory response was induced by intraperitoneal injection of sublethal dose of lipopolysaccharide E. coli (20mg/kg). The survived rats were sacrificed 1 and 7 days after injection. Serum levels of interleucine-2, 12p40, and interferon-γ were evaluated by enzyme-linked immunosorbent assay. Histological examination of abdominal skin slices, stained with hematoxilin and eosin and toluidine blue was performed. Results. The rats developed systemic inflammatory response, which attenuated on the 7th day after lipopolysac- charide injection. No significant changes in skin morphology were found. Skin mast cells demonstrated some morpho- logical and functional changes indicative of active secretion of mediators without activation of degranulation. On the 7th day mast cell cytophysiology had no significant changes compared to the control group. Conclusion. Systemic inflammatory response induced by bacterial lipopolysaccharide does not activate migration of mast cells to skin, but changes their secretory processes by enhancing peace-meal degranulation.

We studied the mechanisms underlying decreased production of epinephrine by adrenal glands in rats developmentally exposed to endocrine disruptor DDT was performed on the basis of assessment of morphology, fine structure, and function of the adrenal medulla and medullary cells. It was found that the main mechanisms of disruptive action of DDT leading to a decrease in epinephrine secretion into systemic circulation are a decrease in the growth rate of the adrenal medulla, a decrease in the number of mitochondria in adrenal cells, especially under the outer cytoplasmic membrane, destructive changes in mitochondria, and a progressive decrease in the synthesis of tyrosine hydroxylase. The decrease in the number of mitochondria and suppression tyrosine hydroxylase synthesis in adrenal cells predominate during the pubertal period, while slowdown of the growth of the adrenal medulla and progressive decrease in the synthesis of tyrosine hydroxylase seem to be the most evident mechanisms after puberty.

We studied histophysiology of the adrenal medulla in adult (70-day-old) male Wistar rats developmentally exposed to low doses of endocrine disruptor DDT. It was found that exposure to DDT during the prenatal and postnatal ontogeny decelerated the development of the adrenal medulla and reduced the synthesis of tyrosine hydroxylase, the rate-liming enzyme of catecholamine synthesis, in chromaffin cells, which led to a decrease in epinephrine secretion into the blood.

Exposure of developing organism to endocrine disrupting chemicals is an emerging scientific problem of wide concern. Dichlorodiphenyltrichloroethane (DDT) is considered to be one of the most wide-spread endocrine disruptors. Exposure of humans to low doses of DDT occurs around the globe. The present study was undertaken to elucidate the role of canonical Wnt-signaling in postnatal morphogenesis of the adrenal medulla in intact and developmentally exposed to DDT rats. The research was performed on male Wistar rats in pubertal (42nd day) and postpubertal (70th day) periods which were exposed to dDt during both prenatal and postnatal and only postnatal development. Adrenal histology showed enlargement of the adrenal medulla due to equal development of chromaffine cells and blood vessels from 42nd to 70th day in the intact rats and slower development of the adrenal medulla in the prenatally and postnatally exposed rats. Age-dependent changes in activation of canonical Wnt-signaling in the intact rats and altered Wnt-signaling along with impaired postnatal morphogenesis of the adrenal medulla in the DDT-exposed rats were found. The data obtained shows that prenatal exposure to DDT unlike postnatal exposure causes more profound decrease in activation of canonical Wnt-signaling in adrenal chromaffine cells and impairs development of adrenal medulla parenchyma.

This study is focused on the role of the canonical Wnt-signaling pathway in morphogenesis and regeneration of the adrenal cortex in rats exposed to the endocrine disruptor dichlorodiphenyltrichloroethane (DDT) during prenatal and postnatal development. Hypoplasia of the zona glomerulosa and, to a greater extent, of the zona reticularis was associated with suppression of canonical Wnt. This data indicates the role of the Wnt-signaling pathway in the development of the zona reticularis. Circulatory disorders in the adrenal cortex led to focal necrosis of the zona fasciculata and subsequent activation of cell proliferation and regeneration, mediated by the inhibition of the canonical Wnt in it. Thus, the disturbance of activation of the canonical Wnt-signaling pathway can be considered as a mechanism of the disrupting effect of DDT in postnatal development.

The role of stable hydrogen isotopes in the thermoregulation and its regulation is poorly studied. We analyzed fluctuations in body temperature and changes in thermoregulation parameters in mice under conditions of reduced deuterium intake. The study was performed on male C57BL/6 mice that consumed water with a low (10 ppm) and normal (146 ppm) deuterium content. In 7 days, fluctuations of body temperature, locomotor activity, and oxygen uptake were assessed. Deuterium depletion in the body reduced the mean value of minute fluctuations of body temperature and the mean spectral density of minute fluctuations in body temperature in the 2-20-min periods. This attested to a stabilizing effect of deuterium depletion on the rhythms of body temperature fluctuations, without significant shifts in the thermogenesis parameters. Thus, drinking water with reduced deuterium content makes them less sensitive to external influences.

We studied functional changes in rat pituitary-thyroid axis after a short-term shift in deuterium body content. Male Wistar rats consumed deuterium-enriched (500,000 ppm) or deuterium-depleted water (10 ppm) for 24 h. Rats of both experimental groups demonstrated elevated concentration of bound with transport proteins thyroxine and reduced level of thyroid-stimulating hormone in serum. No changes in the rate of thyroxine conversion to triiodothyronine were found. Thus, both the increase and reduction of deuterium body content produced similar changes in the function of the pituitary-thyroid axis with primary affection of the thyroid gland, indicative of its higher sensitivity to shift in deuterium levels.

The study examined transcriptional regulation of adrenal zona reticularis development in male Wistar rats exposed to low doses of endocrine disruptor dichlorodiphenyltrichloroethane (DDT) prenatally and postnatally. At pubertal age, zona reticularis demonstrated a retarded growth with a low proliferative activity of its cells. At this age, zona reticularis was characterized with overexpression of β-catenin by steroid-producing cells; a high percentage of cells with membrane and cytoplasmic localization of β-catenin, and reduced number of cells with nuclear β-catenin attesting to insufficient activation of Wnt signaling. Expression of transcriptional factor Oct4 by reticularis cells was down-regulated indicating their diminished proliferative potency. No significant alterations in Sonic Hedgehog expression were observed. Thus, DDT-provoked disorders of transcriptional regulation result in abnormal development of zona reticularis thereby disturbing sexual maturation in males.

We studied secretory activity of adrenal zona fasciculata cells in pubertal rats exposed to low doses of endocrine disrupter DDT during prenatal and postnatal periods and only during postnatal period. In exposed animals, circulatory disturbances leading to degeneration and necrosis of cells as well as regeneration foci were revealed in the outer zona fasciculata. In rats exposed to DDT during the prenatal and postnatal periods, compensatory increase in secretory activity of cells due to increase in mitochondria content was noted in the inner zona fasciculata, which determined elevated serum concentration of corticosterone. In rats exposed to DDT only during the postnatal development, functional activity of zona fasciculata cells was suppressed, which attested to delayed upregulation of secretion.

The aim of the investigation was to study morphological and cytophysiological changes in the adult rat adrenal medulla after prenatal and postnatal exposure to endocrine-disrupting chemical dichlorodiphenyltrichloroethane (DDT). Materials and Methods The experiment was carried out on male Wistar rats (n=30). The rats were exposed to low doses of DDT during prenatal and postnatal development (n=10) and during postnatal development (n=10) only. The average daily intake of DDT by rats was 3.30±0.14 μg/kg. The control (n=10) and experimental animals were sacrificed at the age of 10 weeks (post-puberty), when rat adrenal glands reached their maximum development. Histological samples of the equatorial sections of the adrenal glands were prepared. The adrenal medulla was studied using light microscopy and computer morphometry. Immunohistochemistry was performed to evaluate tyrosine hydroxylase expression in chromaffin cells. Plasma epinephrine content was measured using enzyme-linked immunosorbent assay. Results Postnatal exposure of rats to low doses of the endocrine disruptor was found to interfere with adrenal medulla development and cytophysiology of chromaffin cells. Prenatal and postnatal exposure resulted in more profound delay in adrenal medulla development of adult rats as compared to the values of rats exposed postnatally, which was manifested by reduced area of the adrenal medulla and reduced total area of chromaffin cells in its section. Postnatal exposure is manifested by more significant functional disorders including decreased synthesis of tyrosine hydroxylase enzyme in the cytoplasm of chromaffin cells and elevated number of tyrosine-hydroxylase-negative cells in the medulla section, leading to a decrease in plasma epinephrine concentration. Conclusion Exposure to low doses of DDT in the early stages of development leads to morphological and cytophysiological changes in the adult rat adrenal medulla and, therefore, reduced functional activity of chromaffin cells, which allows considering the endocrine disruptor DDT a potential risk factor disrupting the function of the neuroendocrine system.

Affection of developing organism by endocrine disruptors is an actively studied topic of scientific research in medicine, caused by a progressive increase in the number of diseases and disorders in the development of the reproductive and endocrine systems. Dichlorodiphenyltrichloroethane (DDT) is the most wide-spread endocrine disruptor. Low-dose exposure to DDT disrupts production of sex steroids by poorly known mechanisms. The research was focused on assessment of morphology of adrenal zona reticularis and fine structure of reticularis endocrine cells and changes in their secretory machinery in rats exposed to low doses of DDT during prenatal and postnatal development. The experimental group consisted of the male offspring of dams, who daily consumed solution of o, p-DDT at a concentration of 20 µg/l, from mating until the end of the suckling period in offspring, which then consumed a similar solution of DDT. Daily consumption of DDT by the offspring was 2,90±0,12 µg/kg body weight. These doses corresponds to levels of exposure of humans to DDT with food products taking to account the differences in metabolism of DDT in rats and humans. The control and experimental rats were sacrificed on the 42nd day of postnatal development (pubertal period). Light microscopy of adrenal sections found hypoplasia of zona reticularis in rats after developmental exposure to endocrine disruptor. Electron microscopy revealed prevalence of cells with low lipid content in cytoplasm, less developed endoplasmatic reticulum and Golgi complex and signs of lowered functional activity of mitochondria indicated decreased steroidogenic activity of zona reticularis. These findings explain previously found impaired production of sex steroids in DDT-exposed rats. Electron microscopy also found that disruption of steroid secretion in reticularis cells by DDT led to compensatory enlargement of cells and increase in number of mitochondria per m2 of cytoplasm indicating development of structural support for long-term enhancement of steroidogenic activity.

Sex differences in the expression of iodide transporter SLC5A5 and thyroid peroxidase in thyroid follicular epithelium and thyroid serum profile were assessed in pubertal rats exposed to endocrine disruptor DDT starting from the first postnatal day. It was found that exposure to DDT reduced expression of SLC5A5 in peripheral regions of thyroid lobes in males and in central regions in females. The most pronounced sex differences were observed in thyroid peroxidase expression that remained sensitive to thyroid stimulating hormone regulation in males and lost sensitivity to pituitary stimulation in females after exposure to disruptor, which determines more pronounced hypothyroidism in females.

The structure of the thymus in newborn rats exposed in utero to endocrine disruptor DDT was studied. We found that exposure to low doses of DDT during pregnancy does not disturb thymus formation in the offspring, but leads to changes in its structure than manifested as slower lobulation, wider epithelium-free areas in the cortex, and lower number of thymic corpuscles in the medulla. The results attest to sensitivity of the reticuloepithelial stroma of the thymus to the effects of endocrine disruptor.

We studied the expression of transcriptional factors regulating postnatal morphogenesis of the adrenal zona fasciculata in rats after developmental exposure to endocrine disruptor DDT. It was found that tissue reparation after trophic disorders and cell death triggered by prenatal and postnatal exposure to DDT was accompanied by an increase in the number of Oct4- and Shh-expressing cells forming a pool located outside the regeneration zones and involved in the maintenance of tissue homeostasis in the zona fasciculata. DDT exposure also disrupted the expression of antiproliferative factor Hhex. The data showed that proliferation of fasciculata cells after termination of adrenal cortex growth was downregulated by inhibition of the expression of Oct4 and Shh and suppression of canonical Wnt signaling, i.e. due to a decrease in the reserve cell pool essential for physiological regeneration, which can reduce the reactive potential of the zona fasciculata.

We studied the formation of proliferative response of thymic lymphocytes to T-cell mitogen in rats exposed to endocrine disrupter DDT during prenatal and postnatal ontogeny. Developmental exposure to the endocrine disruptor was found to attenuate proliferative response during puberty and adulthood due to maintenance of higher proliferation rate of thymic lymphocytes in comparison with age-matched controls. Insufficient proliferative response to mitogens in rats developmentally exposed to the endocrine disrupter increases the risk of impairment of cell-mediated reactions of adaptive immunity.

We analyzed the expression of transcriptional factor Oct4 in rat adrenal cortical cells during postnatal development. It was found that Oct4 is expressed by typical cortical cells of the zona glomerulosa, zona fasciculata, and zona reticularis in pubertal and postpubertal periods. The maximum number of Oct4+ cells was found in the zona glomerulosa. An inverse correlation between the number of Oct4+ glomerulosa cells and serum level of aldosterone both in pubertal and postpubertal periods was revealed. After puberty, the number of Oct4+ glomerulosa cells directly correlated with the number of Ki-67+ cells. A hypothesis was put forward that Oct4 is involved in postnatal morphogenesis, regeneration, and functioning of the adrenal cortex.

The effects of endocrine disrupters of transcriptional control of morphogenesis are poorly studied. Changes in the expression of transcriptional factor PRH and proliferation of adrenal cortical cells were analyzed in pubertal and postpubertal rats exposed prenatally and postnatally to low doses of endocrine disrupter DDT. In rats exposed to DDT, the expression of PRH and proliferation of adrenal cortical cells differed from those in control rats. Association between these parameters was weakened in the zona glomerulosa and zona reticularis and was absent in the zona fasciculata. These findings suggest that exposure to DDT in pre- and postnatal periods impairs the regulation of proliferative processes by transcriptional factor PRH in all zones of rat adrenal cortex, which can be a mechanism of the disruptive action of DDT.

Postnatal morphogenesis of the skin and its appendages were studied in the progeny of mice subjected during early gestation period to adoptive transfer of in vivo activated splenic cells. Reversible focal hair loss was observed on postnatal day 17 in the progeny. The number of hair follicles and sebaceous glands, the level of extracellular matrix, and the content of cells in the skin, including mast cells in the derma, decreased, while neutrophils prevailed. Alopecia areata was found in the subsequent generations after mating of male and female progeny. Hence, stimulation of the maternal immune system during early pregnancy led to disorders of the pre- and postnatal morphogenesis of the skin in the progeny and to development of alopecia areata that became an inherited sign.

Transcription factor PRH/Hhex suppresses cell proliferation and contributes to regulation of prenatal and postnatal ontogeny. Neurons of the peripheral nervous system and chromaffin cells were previously considered as non-expressing PRH/Hhex in postnatal development. In our study, the expression of PRH/Hhex in chromaffin cells of rat adrenal glands and association between the decrease of proliferation and activation of PRH/Hhex expression were demonstrated.

The purpose of the present study was to examine morphological and functional alterations in adrenal cortex of rats exposed to low doses of DDT since the first day of postnatal development till puberty. Daily consumption of DDT was 3.71±0.15 μg/kg bw. This level of exposure corresponds with human daily intake of DDT with food products according to maximum permissive levels of food contamination. Production of steroid hormones of the adrenal cortex was evaluated by quantification of aldosterone, corticosterone, estradiol, and estronе serum levels by enzyme-linked immunosorbent assay. Organometry and light microscopy of the adrenal glands were performed. After six weeks of exposure serum concentration of aldosterone was elevated by 50% in average, estradiol - by 25%, estrone - by 29%, but serum level of corticosterone was decreased by 53% compared to the control values. The adrenal glands had decreased weight and reduced cortex width from 897.75±23.31 to 776.25±19.91 μm mainly due to narrowing of reticularis zona by 11.35%. Histological examination also found proportional increase of cell number in mm2 of reticularis zona and therefore found no differences in total endocrine cell count in reticularis zona between the control (14 085.94±704.30) and DDT exposed rats (13 678.20±410.34). Light microscopy revealed hemorrhages between glomerulosa zona and fasciculata zona as well as fasciculate zona and reticularis zona, foci of discomplexity in fasciculate zona, dystrophy and decreased size of fasculata cells. The data obtained demonstrated that low-dose exposure to DDT during postnatal development led to obvious changes in morphology and function of rat adrenal gland. Low doses of DDT disrupt steroid hormone production by all layers of adrenal cortex in puberty. The results show that very low-dose exposure to DDT needs further investigations, and safety of maximum permissible levels of DDT and other endocrine disrupting chemicals in food products should be reassessed.

There is increasing evidence that chronic environmental exposure to DDT and other pesticides play an important role in disregulation of the immune system and increased incidence of autoimmune and allergic diseases. The aim of the research was to investigate whether consumption of low doses of DDT may affect the immune system and change morphology and function of thymus. The research was performed on 42 Wistar rats 80-100gg body weight. Rats were exposed to 1.89±0.086μg/kg DDT per os for 6 and 10 weeks. Histological examination found time-depending acceleration of apoptosis both of lymphocytes and reticuloepitelial cells. After 10 weeks of exposure proliferation of thymocytes was significantly decreased. Concanavalin A-induced mitogenic activity of thymocytes after 10 weeks of exposure to DDT was 6 times higher than the control values. The data obtained showed that even low doses of DDT accelerated thymus aging and modulated proliferation of thymocytes.

Stimulation of maternal immune system in early pregnancy with Concanavalin A, a T-cell mitogen, prior to formation of fetal immune system impairs development of the offspring’s spleen and thymus. Our findings demonstrate that short-term exposure of pregnant murine dams to Concanavalin A, leads to retardation of postnatal development of offspring’s spleen and reduction of lymphocytes count in thymus medulla and accelerated formation of thymic corpuscles.

Differentiation of T cells was studied in the progeny of female C57Bl/6 mice subjected to immunostimulation by administration of concanavalin A or adoptive transfer of concanavalin A-activated splenocytes. Acceleration of T cell maturation during the prepubertal period and decelerated differentiation during the pubertal and post-pubertal periods were revealed.

We studied the possibility of prenatal programming of proliferative potential of thymocytes and splenocytes in the offspring of C57Bl/6 mice via concanavalin A mitogen stimulation of lymphocyte proliferation in maternal organism at the early terms of pregnancy before the formation of immune system organs in the embryo. The offspring demonstrated elevated proliferative activity of thymocytes and splenocytes, enhanced lymphocyte proliferation, and increased production of IL-2 in in vitro response to concanavalin A during the prepubertal period and puberty. Mitogen stimulation of the maternal immune system in early pregnancy results in long-term enhancement of the proliferative potential of thymus and splenic cells in the offspring.

The effects of maternal immune system on the formation and functioning of the fetus is an important problem. Single stimulation of immune system of female C57Bl/6 mice with concanavalin A at the early stages of pregnancy before the formation of fetal immune organs was followed by impairment of antitumor immunity in the progeny by the time of puberty. These changes manifested in the increased survival rate of B16 melanoma, high rate of death of tumor-bearing animals, and low cytotoxic activity of spleen cells on L-929 fibrosarcoma cells.

We studied morphological and functional changes in the thymus and spleen of mouse offspring subjected to single immune stimulation with concanavalin A at early pregnancy terms against the background of systemic inflammatory response. The offspring was characterized less pronounced accidental involution of the thymus, reduced counts of neutrophils in the marginal zone and red pulp of the spleen, mast cell degranulation, and their reduced content in the red pulp.

The time course of morphofunctional changes in the liver, thymus, and spleen was observed in BALB/c mice with Con A-induced experimental hepatitis. The progress of alterative changes in the liver was paralleled by intensification of accidental involution of the thymus. On day 1 of hepatitis development high proliferative and cytostatic activity of splenocytes was paralleled by hemorrhagic necroses and depletion of the peri-arteriolar lymphoid sheaths in the spleen (T-zones), presumably due to migration of activated lymphocytes to the liver and barrier tissues. Later normalization of lymphocyte proliferative activity was paralleled by recovery and hyperplasia of the splenic T-cell zones.

The study was undertaken to measure PAMG-1 (PP 12, IGEBP-1) that is insulin-like growth factor binding protein in blood sera of diabetic patients. We could show a stable significant (10-fold or more in 54% of patients) increase of PAMG-1 concentrations in patients suffering with insulin-dependent diabetes and a moderate (1.5-2 times) increase of PAMG-1 levels in 80% of patients suffering with non-insulin-dependent diabetes. Significant individual differences of DAMG-1 serum concentrations were also demonstrated (10-230 mg/ml in insulin-dependent and 0-360 ng/ml in non-insulin-dependent diabetes).