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Biomedical subjects

L Martini

Publications and source records attributed to L Martini.

At least 55 records · Page 3Linked to original sources
PubMed2001

Low-power diode laser stimulation of surgical osteochondral defects: results after 24 weeks.

The purpose of this study was to evaluate osteochondral lesions of the knee, treated intraoperatively with low-power laser stimulation, and assess results at 24 weeks. Surgery was performed under general anesthesia on six rabbits; a bilateral osteochondral lesion was created in the femoral medial condyles with a drill. All of the left lesions underwent immediate stimulation using the diode Ga-Al-As laser (780nm), whereas the right knees were left untreated as control group. After 24 weeks, the explants from the femoral condyles, either treated employing laser energy or left untreated, were examined histomorphometrically. Results obtained on the lased condyles showed good cell morphology and a regular aspect of the repaired osteocartilaginous tissue.

Animals↗
PubMed2001

Expression and role of functional glucocorticoid receptors in the human androgen-independent prostate cancer cell line, DU145.

We investigated the presence of glucocorticoid receptors (GR) as well as the role of glucocorticoids (Gc) in the control of proliferation of the androgen-independent prostate cancer cell line, DU145. We detected the presence of a specific high affinity binding site (K(d) 2.3 nM) for [(3)H]dexamethasone ([(3)H]Dex) in the cytosolic preparations of DU145 cells; the density of these binding sites is significantly higher than that detected in HA22T/VGH and in HepG2, two hepatoma cell lines classically considered models for the study of GR. Immunocytochemistry studies confirmed the presence of GR in the cytosolic compartment of DU145 cells; GR undergo translocation to the nucleus following exposure to dexamethasone (Dex). The functional activity of GR present in DU145 cells was also studied by analyzing the potency of Dex in inducing chloramphenicol acyltransferase (CAT) activity in DU145 cells transfected with a glucocorticoid/progesterone response element (GRE/PRE) tkCAT plasmid (GRE/PREtkCAT plasmid). The results have shown that Dex stimulates the transcriptional activity of GR in transfected DU145 cells with an EC(50) of 9.65 nM and a maximal induction of sevenfold above basal levels. Finally, a dose-dependent (IC(50) 3.14 nM) decrease of DU145 cell numbers was observed after their exposure to Dex for 4 days; this effect was counteracted by the presence of the steroid antagonist, RU486. In conclusion, the present data suggest a possible role of corticoids in the control of the growth of androgen-independent prostate cancer.

Androgens↗
PubMed2001

The ovariectomized ewe model in the evaluation of biomaterials for prosthetic devices in spinal fixation.

The effect of surgical ovariectomy on cancellous bone was investigated by comparing mechanical properties and microarchitectural characteristics of the lumbar vertebrae in ovariectomized and sham-operated ewes. Eighteen mongrel ewes, 4+/-1 years old, were randomly divided into three groups: 6 animals served as a control group (Baseline), 6 were bilaterally ovariectomized (OVX), and the others were used as a sham-operated group (SHAM). OVX and SHAM ewes were euthanized 24 months after surgery; the L5 vertebrae were processed for mechanical and histomorphometric analyses. Maximum load, maximum strength (p<0.0005) and elastic modulus (p <0.005) decreased by about 28% in the OVX group in comparison with the other groups. In the OVX group, vertebral cancellous bone volume, trabecular thickness and trabecular number decreased by about 32% (p<0.0005), 15% (p=0.001) and 20% (p=0.019), respectively. An overall decrease in the bone turnover rate of the OVX group was registered in terms of bone formation rate (p=0.007) and activation frequency (p<0.0005). The variations observed in cancellous bone mechanics and histomorphometry would suggest the development of an osteopenic state in ewe vertebrae at 24 months. Such findings may be useful for future experimental investigations on biomaterials and prosthetic devices to be implanted in the osteopenic spine.

Animals↗
PubMed2001

Sheep model in orthopedic research: a literature review.

The aim of the study reported here was to provide some basic and general information on the suitability of an experimental sheep model for conducting in vivo orthopedic studies. The authors have classified the fundamental aspects that should be carefully evaluated when using sheep as an experimental model in orthopedic research: factors strictly related to bone anatomy and formation; and factors strictly affecting bone physiology, such as gastrointestinal mineral and vitamin absorption, and reproductive cycle. Future investigations should address all of the aspects highlighted, since there is no animal with the same anatomic, biochemical, physiologic, and biological characteristics as those of human beings. Moreover, useful data for treating orthopedic patients are based not only on good planning and study design, but also on perfect knowledge of the animal used and the differences between the model and the human being. The authors hope that this report will contribute to extrapolation of reliable data for use of sheep in the orthopedics field.

Animals↗
PubMed2000

Leptin: a possible link between food intake, energy expenditure, and reproductive function.

Several regulatory substances participate in the regulation of both food intake/energy metabolism and reproduction in mammals. Most of these neuropeptides originate and act in the central nervous system, mainly at specific hypothalamic areas. Leptin represents a signal integrating all these functions, but originating from the periphery (adipose tissue) and carrying information mainly to central structures. Observations in rodent models of leptin deficiency have suggested that leptin participates in the control of reproduction, in conjunction with that of food intake and energy expenditure. Indeed, leptin administration resulted in the restoration of normal body weight, food intake, and fertility in the ob mouse, lacking circulating leptin. Specific targets of leptin in the hypothalamus are neurons expressing neuropeptide Y, proopiomelanocortin and gonadotropin-releasing hormone, but the presence of leptin receptors in peripheral reproductive structures suggests that leptin might also act at these sites. Human obesity is often associated with reproductive disturbances. The situation in humans is more complex than in the animal models of leptin deficit and the presence of leptin resistance in these subjects is suggested. In conclusion, leptin fits many requirements for a molecule linking the regulation of energy balance and the control of reproduction.

Animals↗
PubMed2000

Motoneuronal cell death is not correlated with aggregate formation of androgen receptors containing an elongated polyglutamine tract.

Spinal and bulbar muscular atrophy (SBMA) is associated with an abnormal expansion of the (CAG)(n)repeat in the androgen receptor (AR) gene. Similar mutations have been reported in other proteins that cause neurodegenerative disorders. The CAG-coded elongated polyglutamine (polyGln) tracts induce the formation of neuronal intracellular aggregates. We have produced a model to study the effects of potentially 'neurotoxic' aggregates in SBMA using immortalized motoneuronal cells (NSC34) transfected with AR containing polyGln repeats of different sizes [(AR.Q(n = 0, 23 or 46)]. Using chimeras of AR.Q(n) and the green fluorescent protein (GFP), we have shown that aggregate formation occurs when the polyGln tract is elongated and AR is activated by androgens. In NSC34 cells co-expressing the AR with the polyGln of pathological length (AR.Q46) and the GFP we have noted the presence of several dystrophic neurites. Cell viability analyses have shown a reduced growth/survival rate in NSC34 expressing the AR.Q46, whereas testosterone treatment partially counteracted both cell death and the formation of dystrophic neurites. These observations indicate the lack of correlation between aggregate formation and cell survival, and suggest that neuronal degeneration in SBMA might be secondary to axonal/dendritic insults.

Animals↗
PubMed2000

Evaluation of pain and stress levels of animals used in experimental research.

This paper represents a contribution to researchers employing "in vivo" models in experimental surgery in order to obtain more reliable results in accordance with current legislation and Russel's "three R" statement: refinement, reduction, and replacement. After general consideration about the definition of pain and stress concerning laboratory animals, the authors suggest making an evaluation of the experimental protocol before approval by the local committee to allow assessment in terms of the costs/benefits of experimental research employing live animals.

Animals↗
PubMed2000

Aging in peripheral nerves: regulation of myelin protein genes by steroid hormones.

The process of aging deeply influences morphological and functional parameters of the peripheral nerves. Interestingly, recent observations performed in our laboratory on the rat sciatic nerves have indicated that the deterioration of myelin occurring in the peripheral nerves during aging may be explained by the fall of the messenger levels of the major peripheral myelin proteins (glycoprotein Po, myelin basic protein and peripheral myelin protein 22). At least in the case of the Po, the low levels of its messengers and of the protein itself found in aged animals are increased by the treatment with a physiological progesterone derivative like dihydroprogesterone. It has also been found that in normal adult male rats the levels of the messengers for Po in the sciatic nerve are increased by progesterone, dihydroprogesterone and tetrahydroprogesterone; surprisingly, the gene expression of peripheral myelin protein 22 is stimulated only by tetrahydroprogesterone. These observations have been confirmed in parallel studies performed on Schwann cell cultures. Since tetrahydroprogesterone does not bind to the progesterone receptor but is a ligand for the GABAA receptor, the hypothesis has been put forward that part of the steroidal effects reported might occur not through the classical progesterone receptor, but rather via an interaction with the GABAA receptor. In other experiments it has been found that the gene expression of Po may be decreased by orchidectomy and restored by treatment with the androgen dihydrotestosterone. Altogether, these observations suggest the future use of physiological and/ or synthetic steroid hormones as a possible therapeutic approach for some pathological situations occurring in peripheral nerves during aging and demyelinating diseases.

Aging↗
PubMed2000

Immortalized luteinizing hormone-releasing hormone neurons show a different migratory activity in vitro.

The development of two cell lines (GT1 and GN) of immortalized LHRH neurons has allowed an accurate study of the mechanisms controlling the synthesis and the secretion of LHRH. These cell lines, obtained in mice by genetic targeted tumorigenesis, retain many of the phenotypic characteristics of LHRH neurons. Of interest, GT1 cells derive from an hypothalamic tumor, whereas GN cells were obtained from a tumor localized in the olfactory bulb. The different origin of these cell lines lead to hypothesize that they might represent hypothalamic postmigratory neurons (GT1 cells), or LHRH neurons blocked at an early stage of their migration (GN cells). Using different experimental procedures, we found that the two cell subclones GT1-7 and GN11 express a different morphology and migratory behavior in vitro. In particular, we found that GN11 cells, but not GT1-7 cells, show the morphological shape of migrating neurons. When analyzing the spontaneous motility we found that only GN11 cells express a high capacity of migrating in a matrix of collagen gel. Moreover, in a chemomigratory assay GN11 cells did show a significant response to the chemotactic stimulus represented by the FBS. On the contrary, GT1-7 cells show very low spontaneous motility and appear insensitive to the FBS stimulus. These results suggest that the simultaneous use of the GT1-7/GN11 cells may represent an experimental tool for screening the factors possibly involved in the control of the migratory processes of LHRH neurons in normal and in pathological conditions, such as those due to their impaired migration, like it happens in Kallmann's syndrome.

Animals↗
PubMed2000

Corticosteroids regulate the gene expression of FGF-1 and FGF-2 in cultured rat astrocytes.

The present data show that the gene expression of FGF-1 and FGF-2 is regulated by corticosteroids in rat type 1 astrocytes. In particular, the gene expression of FGF-1 is modulated by corticosteroids acting both on type I (minerocorticoid) and type II (glucocorticoid) receptors. In fact, at short times of exposure (2 h) a slight decrease in FGF-1 mRNA levels is induced by deoxycorticosterone, a steroid able to interact with the type I receptors; a similar effect is observed at 6 h following exposure to corticosterone or its 5alpha-reduced metabolite, dihydrocorticosterone. Conversely, at longer times of exposure (24 h) corticosterone is able to strongly increase FGF-1 mRNA levels. Both effects of corticosterone (inhibition and stimulation) were duplicated by dexamethasone, indicating that both effects occur via the type II receptors. Interestingly, the 5alpha-3alpha-reduced metabolite of deoxycorticosterone, tetrahydrodeoxycorticosterone, which does not interact with either corticosteroid receptors, is able to stimulate (at 6 and 24 h of exposure) the gene expression of FGF-1. It is possible that this effect might be induced via the GABA(A) receptor, since muscimol, an agonist of this receptor, exerts a similar effect. The situation is different in the case of FGF-2. The mRNA levels of this growth factor are only stimulated by steroids interacting with type II receptors. Altogether, these observations indicate that corticosteroids modulate the levels of FGF-1 and FGF-2 gene expression in astroglial cells by interaction with classical (type I and II) or nonclassical (GABA(A) receptor) steroid receptors.

Adrenal Cortex Hormones↗
PubMed2000

Factors released by rat type 1 astrocytes exert different effects on the proliferation of human neuroblastoma cells (SH-SY5Y) in vitro.

Brain metastases derived from abdominal neuroblastoma are an uncommon complication of this tumour; however, an increase in their occurrence has recently been reported. In the present study, we have investigated the influence of factors derived from central nervous system glial cells on the proliferation of human neuroblastoma cells (SH-SY5Y) in vitro. Co-culture experiments show that a 24-h exposure to factors released by type 1 astrocytes (A1) may induce a significant decrease in [(3)H]thymidine ([(3)H]TdR) incorporation by SH-SY5Y cells. This effect was not duplicated by fresh A1-conditioned medium (A1-CM); A1-CM became active only when it was heated or frozen. In contrast to this short-lived inhibitory effect, long-term treatment (3, 6 and 9 days) with A1-CM produced a significant and dose-dependent increase in SH-SY5Y cell number. Immunoneutralisation of A1-CM with an anti-transforming growth factor-beta antibody eliminated the inhibitory effect on [(3)H]TdR uptake in SH-SY5Y cells, but did not affect the increased number of viable cells observed after long-term treatments. In conclusion, these results showed that factor(s) released by A1 may affect the proliferation/survival of a human neuroblastoma cell line in vitro inducing: (a) a short transient negative effect on DNA synthesis and (b) an overall sustained trophic action. These results are suggestive of a possible role of glial cells in the establishment of brain metastases of neuroblastomas.

Animals↗
PubMed2000

Thick cutaneous malignant melanoma: a reappraisal of prognostic factors.

The prognosis of patients with thick (>3 mm) cutaneous malignant melanomas is generally poor; however, some cases survive far longer than expected. Thus tumour thickness cannot serve as the only predictor of disease course in the individual patient. The aims of the current study were to evaluate the clinical outcome of patients with thick (>3 mm) cutaneous melanoma and test the prognostic value of a series of clinicopathological parameters on disease-free and cause-specific survival. We retrospectively evaluated 140 patients with stage I cutaneous melanoma >3 mm in thickness. Disease-free and cause-specific survival rates (Kaplan-Meier method) were compared using the log rank test. A multivariate analysis (Cox proportional hazards model) was used to determine the independent effect of each variable on prognosis. The overall 5-year and 10-year disease-free survival rates were 35.5% and 29.3%, respectively, whereas the overall 5-year and 10-year cause-specific survival rates were 55.3% and 47.7%, respectively. In the univariate analysis, the following factors were found to be significantly associated with the disease-free and cause-specific survival: tumour thickness, mitotic rate/mm2, type of invasive front, ulceration, thickness of the nodular component and predominant cell type. In addition, the presence of vascular invasion was significantly correlated with the risk of metastases but not with survival. In the multivariate analysis (Cox proportional hazards model), only tumour thickness (both as a continuous variable and >7.5 mm), infiltrating invasive front, presence of ulceration and mitotic rate/mm2 (both as a continuous variable and >10 mitoses/mm2) were significant independent predictors of poorer clinical outcome.

Adult↗
PubMed2000

The ovariectomised sheep as a model for testing biomaterials and prosthetic devices in osteopenic bone: a preliminary study on iliac crest biopsies.

A histomorphometric and ultrastructural evaluation on sheep iliac bone was performed. Six sheep were ovariectomised (OVX Group) and 6 were left intact (Sham-aged, Control Group). An iliac crest biopsy was performed randomly in 6 animals at the beginning of the study, then, in all the animals, after 12 and 24 months. A significant decrease in trabecular bone volume, trabecular thickness (p<0.0005) and cell volume (p<0.005) was observed in OVX animals. A modest decrease in trabecular number and osteoid thickness together with an increase in trabecular separation were observed in OVX animals at 12 and 24 months. The osteoid volume showed a significant difference (p<0.05) between the groups. In OVX animals, at 12 months, Scanning Electron Microscopy revealed an enlargement of the trabecular space and a progressive replacement of bone matrix with adipose tissue. These signs were accentuated at 24 months. In conclusion, OVX sheep showed a loss of trabecular bone starting at 12 months after ovariectomy. The developed osteopenic state may be considered as a useful tool when doing research on biomaterial osteointegration.

Analysis of Variance↗
PubMed2000

A resorbable biomaterial shaped as a tubular chamber and containing stem cells: a pilot study on artificial bone regeneration.

In a previous study, we showed how healing of non-union defects in rabbit radii can be achieved by means of a tubular resorbable chamber, in comparison with untreated defects. In the present study, we placed bone marrow stem cells inside the chamber. Bone marrow was obtained by percutaneous aspiration from the iliac crest in 9 adult New Zealand rabbits. Stem cells were separated by the centrifugation technique. In the same animals, a defect of 10 mm was created in both radii. On the left side, the defect was treated with the poly-DL-Lactide chamber, in which a suspension of autologous cells was injected; on the right side, only autologous cells were used. Radiological and histomorphometric data were compared within this study as well as with the results of our previous study. At 3, 6 and 9 months, there was no healing on the right side..On the left side, progressive bone formation with reunion of the stumps was observed in the chamber. We conclude that stem cells can accelerate bone healing when contained in the tubular chamber.

Animals↗
PubMed1999

Steroid metabolism and effects in central and peripheral glial cells.

Hormonal steroids participate in the control of a large number of functions of the central nervous system (CNS); recent data show that they may also intervene at the level of the peripheral nervous system (PNS). Both the CNS and the PNS metabolize endogenous as well as exogenous steroids; one of the major enzymatic system is represented by the 5alpha-reductase-3alpha-hydroxysteroid complex. This is a versatile system, since every steroid possessing the delta 4-3keto configuration (e.g., testosterone, progesterone, deoxycorticosterone) may be a substrate. High levels of 5alpha-reductase are found in the white matter of the CNS and in purified myelin. The observation that, in addition to neurons, glia may be a target for steroid action is an important recent finding. The effects of progesterone, testosterone, corticoids, and their respective 5alpha and 3alpha-5alpha derivatives on the expression of glial genes are presented and discussed. It has also been found that progesterone and/or its 5alpha-reduced metabolites increase the mRNA for the two major proteins of peripheral myelin, the glycoprotein Po and the peripheral myelin protein 22, in the sciatic nerve of normal and aged animals and in Schwann cells. The hypothesis has been put forward that glycoprotein Po might be under the control of progestagens acting mainly via the progesterone receptor, and that peripheral myelin protein 22 might be controlled via an interaction of steroids with the gamma-aminobutyric acid (GABA)ergic system. It is known that tetrahydroprogesterone, the 3alpha-5alpha-reduced metabolite of progesterone, interacts with the GABA(A) receptor. Our recent data show that several subunits of this receptor are present in sciatic nerve as well as in Schwann cells that reside in this nerve. These data open multiple possibilities for new therapeutic approaches to demyelinating diseases.

Animals↗