Prenatal cigarette smoke exposure slightly alters neurobehavioral development in neonatal rats: Implications for developmental origins of health and disease (DoHAD).

Numerous studies indicate that smoking during pregnancy exerts harmful effects on fetal brain development. The aim of this study was to determine the influence of maternal smoking during pregnancy on the early physical and neurobehavioral development of newborn rats. Wistar rats were subjected to whole-body smoke exposure for 2 × 40 min daily from the day of mating until day of delivery. For this treatment, a manual closed-chamber smoking system and 4 research cigarettes per occasion were used. After delivery the offspring were tested daily for somatic growth, maturation of facial characteristics and neurobehavioral development until three weeks of age. Motor coordination tests were performed at 3 and 4 weeks of age. We found that prenatal cigarette smoke exposure did not alter weight gain or motor coordination. Critical physical reflexes indicative of neurobehavioral development (eyelid reflex, ear unfolding) appeared significantly later in pups prenatally exposed to smoke as compared to the control group. Prenatal smoke exposure also resulted in a delayed appearance of reflexes indicating neural maturity, including hind limb grasping and forelimb placing reflexes. In conclusion, clinically relevant prenatal exposure to cigarette smoke results in slightly altered neurobehavioral development in rat pups. These findings suggest that chronic exposure of pregnant mothers to cigarette smoke (including passive smoking) results in persisting alterations in the developing brain, which may have long-lasting consequences supporting the concept of developmental origins of health and disease (DoHAD).

Examination of PACAP38-like immunoreactivity in different milk and infant formula samples.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with special importance in reproductive and developmental processes. PACAP is found in two bioactive forms: PACAP27 and PACAP38. Recently, we have described that PACAP38 is present in high levels in the milk of human and ruminant animals. Breastfeeding is of utmost importance in proper nutrition of the newborn, but artificial nursing with infant formulas is necessary when breastfeeding is not available. Composition of the breast milk varies during the whole period of nursing and it shows differences at the beginning (foremilk) and the end of an actual suckling (hindmilk). The aim of this study was to investigate PACAP38-like immunoreactivity (PACAP38-LI) in different milk and infant formula samples by radioimmunoassay and to prove the presence of PACAP38 in the infant formula by mass spectrometry. We found similar PACAP38-LI in human mature foremilk and hindmilk samples, in the fresh and pasteurized cow milk and also in formulas. However, we found significantly higher PACAP38-LI in the hypoantigenic formula undergoing extensive hydrolysis compared to the non-hypoantigenic ones. Our results suggest that PACAP38 is relatively stable in the milk and it can withstand the manufacturing processes.

Alterations of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity in the human plasma during pregnancy and after birth.

BACKGROUND: Since its discovery, several distinct effects of pituitary adenylate cyclase activating polypeptide (PACAP) have been established - predominantly in animal studies - in the nervous system, various peripheral organs as well as in the endocrine regulation. It is unknown whether PACAP has any effect on human pregnancy regarding either utero-maternal or perinatal aspects of the gestation. AIM: We investigated alterations of PACAP38-like immunoreactivity (PACAP38-LI) in the human plasma throughout normal pregnancy, during and after delivery, and its level in the umbilical vessels, as well as in the peripheral blood of term healthy newborns. MATERIALS AND METHODS: A 2 ml blood sample was used for each test, PACAP38-LI was determined by radioimmunoassay. RESULTS: In the 2nd and 3rd trimester significant elevation was observed in the PACAP38-LI compared to the earlier gestation and non-pregnant conditions. During delivery its level significantly decreased and returned to the original values 3 days after birth. In the neonates PACAP38-LI level of the peripheral blood was similar to that of healthy adults, but umbilical arteries and veins contained significantly lower concentrations of PACAP38-LI. Besides, the levels were lower in the umbilical vein compared to the artery. CONCLUSIONS: PACAP38-LI levels show sensitive change during normal pregnancy and delivery. Our findings suggest that the fetal organs actively synthesize PACAP. Further investigations are required to elucidate the physiological importance of the alterations observed.

Epidural malignant lymphomas of the spine: collected experiences with epidural malignant lymphomas of the spinal canal and their treatment.

STUDY DESIGN: Retrospective study of 13 patients treated by the authors. OBJECTIVE: To examine the course of the disease of malignant lymphoma (ML) presenting in the epidural area of the spine. SETTING: Department of Neurosurgery, Third Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. SUBJECTS AND METHODS: The epidural presentation in eight patients was heralded by motor signs (paraparesis and plegia), in one by a lesion of the posterior columns of the spinal cord (ataxia), and in three by pain. One patient was free of complaints and symptoms. The affected epidural area was diagnosed previously by myelography and computerized tomography (CT), and later by magnetic resonance (MR), over the course of which the location was verified as thoracic in eight patients, cervical in one, and lumbar in four. The authors recommended surgical intervention in 9 out of 13 cases, in seven cases of Hodgkin's and six cases of non-Hodgkin's lymphoma. Seven patients were treated for recognized manifestations of malignant lymphoma while six were diagnosed by intraoperative-histological examination. RESULTS AND CONCLUSION: The decompression operations for tumors resulted in limited improvement in seven patients (reduction in pain and return of ability to walk). Four patients were not operated on, two of which had significant improvement in their neurological symptoms. Paraparesis remained unchanged in one patient. One patient remained symptom-free. The authors emphasize the importance of interdisciplinary consultation and weighing individual priorities in the indications for operation on epidural ML.

Dual regulation of leptin secretion: intracellular energy and calcium dependence of regulated pathway.

Rodent leptin is secreted by adipocytes and acutely regulates appetite and chronically regulates body weight. Mechanisms for leptin secretion in cultured adipocytes were investigated. Acutely, energy-producing substrates stimulated leptin secretion about twofold. Biologically inert carbohydrates failed to stimulate leptin secretion, and depletion of intracellular energy inhibited leptin release. There appears to be a correlation between intracellular ATP concentration and the rate of leptin secretion. Insulin increased leptin secretion by an additional 25%. Acute leptin secretion is calcium dependent. When incubated in the absence of calcium or in the presence of intracellular calcium chelators, glucose plus insulin failed to stimulate leptin secretion. In contrast, basal leptin secretion is secreted spontaneously and is calcium independent. Adipocytes from fatter animals secrete more leptin, even in the absence of calcium, compared with cells from thinner animals. Acute stimulus-secretion coupling mechanisms were then investigated. The potassium channel activator diazoxide and the nonspecific calcium channel blockers nickel and cadmium inhibited acute leptin secretion. These studies demonstrate that intracellular energy production is important for acute leptin secretion and that potassium and calcium flux may play roles in coupling intracellular energy production to leptin secretion.

Fetal type lymphocytes in insulin dependent diabetes mellitus.

CD5+ B and gamma/delta T lymphocytes constituting a major population in the fetus and newborn infant, represent two small subsets of the B and T lymphocyte compartment in healthy adults. There is evidence for their potential involvement and relative expansion in autoimmune disorders. In insulin-dependent diabetes mellitus (IDDM) CD5+ B lymphocyte counts have been found to be increased or normal. The aim of our study was to determine the percentage of both "fetal type" lymphocyte subsets in peripheral blood of 22 recently diagnosed children with IDDM, in that of 13 high risk subjects (islet cell antibody (ICA) positive non-diabetic Ist degree relatives of diabetic children) and in 43 healthy controls. The percentage of gamma/delta TCR+ cells and of CD5+ B lymphocytes was found to be significantly (p < 0.0001 and p = 0.03, respectively) higher in the diabetic and prediabetic groups as compared to controls. Young children with IDDM associated antibodies carry a higher risk of developing clinical IDDM than older individuals. In our hands, the percentage of both CD5+ B and gamma/delta T lymphocytes was higher in the younger population. However, age-dependent decrease for both lymphocyte subpopulations in IDDM-prediabetic patients was less than in healthy controls. Since the above subpopulations are supposed to play a role in immune response to conserved structures, these observations would suggest a higher capacity of older individuals to 'natural autoimmunity" and would explain at least in part the increased risk of antibody positive young children to develop IDDM.

[Sonography of experimental hypovascularized kidney tumors]. / Sonographie von experimentellen hypovaskularisierten Nierentumoren.

The authors studied the sonographic features of Vx2-renal carcinomas in rabbits induced by the Vargha method. The series consisted of 81 rabbits with Vx2-renal carcinomas, 17 controls, five rabbits with retrorenal Vx2-carcinomas and 56 rabbits with gluteal Vx2-carcinomas. In 70.8% ultrasound showed changes on the tenth day and in 98.6% on the 14th day; usually these were of low echogenicity, in 32.4% there was mixed echogenicity and in a few a highly echogenic pattern was found. After 21 days the ultrasound pattern became increasingly of poor echogenicity. 41.3% showed of necrosis by 14 days and after 21 days 100% were necrotic. On the seventh day Vx2-renal carcinomas were mostly hyper-reflective.

The effect of ipriflavone treatment on osteoporosis induced by immobilization.

The purpose of these experiments was to study the effect of Ipriflavone (7 isopropoxy-isoflavone) on the osteoporosis induced by immobilization. The immobilization was produced by plaster cast of the right hind limb in young and old rats. Ipriflavone was administered via a gastric tube in a daily dose of 40 mg/kg body weight for 8 weeks. On the basis of histological and histomorphometric examinations of the tibia, results of Ipriflavone treatment are the following: 1) The decrease in the density and volume of spongy trabecules was less apparent in both meta- and diaphysis; 2) The amount of persisting cartilage core and structural rarefication of trabecules were diminished; 3) In the metaphysis osteoblastic activity was considerably enhanced; 4) Bone resorption and cortical thinning were decreased; 5) Bone remodeling was increased subperiosteally and to small extent also endosteally; 6) The treatment did not prevent the development of osteoporosis but significantly diminished it.

Morphological studies on the articular cartilage of old rats.

Age-dependent morphological alterations of the tibial articular cartilage were studied in 26-month-old Wistar rats of both sexes. Young and adult rats (6 and 10 months of age, respectively) served as a basis for comparison. Light microscopic histology, polarization optical analysis (toluidine-blue staining with or without the addition of 0.2, 0.4 or 0.8 M MgCl2, as well as after phenol reaction) as well as transmission electron microscopy were applied. The main observations are: (1) According to the histological findings, the proportion of the zones changes with age; the subchondral bone layer becomes wider and separated to a certain extent, while the fibres become demasked. (2) Polarization microscopy revealed a disorientation of both the proteoglycane (PG) and collagen molecules; considering the available biochemical data, this phenomenon involves both quantitative and structural changes, as well as differences in the localization of the PG and collagen molecules. (3) Electron microscopy also supports the structural alterations of the collagen (thin and thick, as well as non-striated, fragmented fibres). Cellular alterations are also observed parallel with the changes of the matrix (cell organelles occur less frequently, signs of degeneration and disintegration, rupture of the plasma membrane, as well as accumulation of lipid-bodies can be seen. On the basis of the findings, one can consider the articular cartilage in the old rats as a tissue which is still in equilibrium, however, aged chondrocytes with decreased function become predominant in it. This state can be modified into a pathological one by various mechanical, endocrinological, iatrogenic, post-traumatic, etc., influences through the alterations of the cell-matrix interactions.

Radiological investigation of alterations in the rat femur after long-term immobilization.

The right hind limb of female rats was immobilized by plaster cast. Following 8 weeks of immobilization the alterations were compared with either the contralateral extremity of the same rat or with the extremities of non-immobilized animals. The femurs were investigated by microradioscopic, morphometric, densitometric and atom absorption methods. The results obtained have unequivocally shown that long-term immobilization by plaster cast leads to development of osteoporosis in the rat. Even though no considerable loss of calcium could be demonstrated when calculated in terms of unit layer thickness quantitative analysis of the bone revealed a high degree of osteopenia.

Effect of plaster-cast immobilization on the bone.

Plaster-cast of the right hind limb resulted in immobilization osteoporosis in rats. The alteration was characterized by loss of the bony substance as well as by a partial transformation of lamellar bone to primordial osseous tissue. In the basis of histological and histomorphometric findings, an accelerated osteoclastic activity, an increased osteocytic osteolysis and a decreased ossification are responsible for the observed changes.

Arthropathy in haemodialysed patients.

The joint disorders associated with osteodystrophy of 124 regularly haemodialysed patients are reviewed. The most common signs and symptoms of uraemic osteoarthropathy are summed up. It is pointed out that in osteoarthropathy accompanying chronic renal failure or haemodialysis the bones are generally affected first, arthropathy being secondary to this process. In addition to the classic signs and symptoms of arthropathy (calcification, pain, stiffness) capsulitis, carpal tunnel syndrome and in 3 cases avascular necrosis were observed. The laboratory findings included hypocalcaemia, hyperphosphataemia and hypersecretion of parathormone. The current preventive and therapeutic measures are reviewed and in this context the benefits of combined local lidocaine, and steroid iontophoresis are emphasized in the light of personal observations.

[Effect of chronic vitamin D deficiency on joint cartilage]. / Wirkung des chronischen D-Vitaminmangels auf den Gelenkknorpel.

The effect of six-months rachitic diet on the articular cartilage of 12 white Whistar male rats has been studied using light, polarisation, and electronmicroscopes. On the basis of our observations radical changes could be noticed. The intracellular accumulation of glycogen and lipid and the necrosis of cells in the proof/inner/zone indicate the modifications of the cell's structure. The effect of permanent diet on the ground substance of articular cartilage was identified by irregular collagen fibers, and quantitative and qualitative changes of GAGs. On the basis of several author's argumentations it can be supposed that different illness/insufficiency of liver and kidney, and disturbance of resorption in human/can induce similar changes of articular cartilage which was produced by a long term rachitic diet. The cytological picture after long lasting rachitic diet is comparable with the arthrosis.

Experimental calcipenic osteopathy.

Calcipenic osteopathy was used as a model, in order to reveal the diagnostic value and capacity of the noninvasive radiological methods (microradioscopy, densitometry, and Roentgen-morphometry), in comparison with the results of histological, histomorphometrical, and atomic absorption methods. The study proved that calcipenic diet causes an osteoporosis in the experimental animals. The alterations observed meet both the histological and radiological criteria.

Alterations of the connective tissue in nude mice.

The epiphyseal cartilage of nude mice was studied by light and electron microscopy. The resting and maturation zones become narrow and mineralization of the ground substance starts already in the zone of proliferation. Electron microscopy reveals signs of degeneration in the chondrocytes of this latter zone. An increased osteoclast activity can be observed in the metaphysis. The alterations may be due to a decrease in T-cell-mediated immunoreactivity of nude mice, as well as to an increased production of the osteoclast-activating factor, which might be attributed, among other things, to the B lymphocytes or macrophages.