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Biomedical subjects

L Aloe

Publications and source records attributed to L Aloe.

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

[Neurotrophic factors and brain damage in hypoxic-ischemic encephalopathy: a role of nerve growth factor?].

Hypoxic-ischaemic damage in perinatal brain is a major risk factor of a variety of serious human neurological disorders. The mechanisms leading to neuronal damage and death remain largely unknown, but animal models indicated that cell death via apoptotic mechanism(s) might be one important aspect of these events. Neurotrophic factors are protein molecules produced and released by several tissues which seem to play a crucial role not only in growth, differentiation and function of brain neurons, but also in the mechanisms of neuronal death. Indeed, experiments carried out on animal models support the hypothesis that the neurotrophins NGF and BDNF are able to prevent and/or reduce neuronal death induced by hypoxic-ischaemic events. In this brief review, the established and emerging evidences supporting this hypothesis are presented and discussed.

Brain Damage, Chronic↗
PubMed2001

Developmental profile of serum nerve growth factor levels in Rett complex.

Rett syndrome (RS) is a progressive neurodevelopmental disorder predominant in females, characterised by mental deficiency, stereotyped hand-washing and apraxia. Notwithstanding the recent identification of the MECP2 gene likely involved in the pathogenesis of SR, the neurobiological bases of this syndrome are still largely unknown. Converging evidence shows that the brain levels of nerve growth factor (NGF), a neurotrophin regulating the development and functioning of central cholinergic neurons, are decreased in RS girls. In this study, the serum levels of NGF were measured in classic RS, in the preserved speech variant (PSV) and in normal controls. Overall analysis failed to evidence significant differences among the three groups. However, whereas NGF levels increased significantly with age in controls, the opposite profile was observed in classic RS, with a progressive age-dependent decrease of NGF. In PSV subjects NGF levels remained constant with age. These findings strengthen the hypothesis of NGF involvement in the pathogenesis of RS.

Adolescent↗
PubMed2000

RT-PCR ELISA method for the analysis of neurotrophin mRNA expression in brain and peripheral tissues.

The levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in brain and periphery are susceptible to changes during development and as result of different physiopathological conditions, such as stress and aging and during the onset and progression of neurological and autoimmune diseases. Despite the sensitive methods for measurement of neurotrophin protein levels in different tissues, no easily applicable methods to evaluate changes in the level of NGF and BDNF mRNA expression within physiological range have been described. This study reports the development of a reproducible and simple procedure for measurement of neurotrophin mRNA expression in brain and peripheral tissues based upon an enzyme linked immunosorbent assay (ELISA) detection system of reverse transcriptase-polymerase chain reaction (RT-PCR) products. The major advantages of this RT-PCR ELISA procedure is to allow the co-amplification of diverse mRNAs starting from small amounts of tissues; to contemporaneously test a large number of samples; to be rapid and to use only commercial reagents and widely available equipment. The procedure could also be useful in studies addressed to measure the pattern of expression of molecules involved in the pathogenesis of neurodegenerative and inflammatory diseases, such as neuropeptides and cytokines.

Animals↗
PubMed2000

Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural and biochemical analysis.

In this study we investigate the neurotoxic action of Cisplatin (6 micrograms/g body weight for 5 treatment cycles during 15 weeks with a total dose of 30 micrograms/g), an antitumor drug, and its effect on the level of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in peripheral tissues. We found that Cisplatin in adult rodents impairs peripheral sensory function and both sympathetic and sensory peripheral innervation as shown by the hot-plate response, catecholamine distribution and substance P immunoreactivity respectively. These changes are associated with decreased NGF in intestine, paws, and bladder while NGF increased in the spinal cord. Also BDNF decreased in bladder and paws and increased in spinal cord and intestine. To further investigate the role of NGF in the pathogenesis of Cisplatin-induced peripheral neuropathies a group of animals was injected with NGF (1 microgram/g every 4 days for 4 times) following Cisplatin treatment and evaluated for sensory function, sympathetic and sensory innervation and BDNF levels. Data demonstrated that exogenous NGF administration is able to restore biochemical, structural and functional changes induced by Cisplatin. These findings suggest that the reduction of NGF availability could be a cause of Cisplatin-induced peripheral neuropathies and that NGF exogenous administration could prevent or reduce Cisplatin neurotoxicity also in cancer patients, reducing the side effects of chemotherapy.

Animals↗
PubMed2000

NGF, a useful tool in the treatment of chronic vasculitic ulcers in rheumatoid arthritis.

Vasculitic necrosis and ulceration of the skin are frequent complications of connective tissue diseases and are very difficult to heal. We treated chronic vasculitic leg ulcers in rheumatoid arthritis and systemic sclerosis by topical application of nerve growth factor (NGF). In all patients with rheumatoid arthritis, NGF led to rapid healing, whereas less striking results were obtained in patients with systemic sclerosis. The efficacy of NGF could be due to its promoting activity on keratinocytes proliferation and vascular neoangiogenesis. We suggest that topical application of NGF could represent a powerful pharmacological tool for the treatment of vasculitic ulcers.

Aged↗
PubMed2000

NGF expression in the developing rat brain: effects of maternal separation.

A number of studies have shown that mothering style in rodents can produce neuroendocrine, neurochemical and behavioural changes in the adult, although the basic mechanisms initiating this cascade of events still need to be investigated. Long term changes in neuronal function might be due to alterations in the expression of neurotrophins which have been shown to promote neuronal survival, differentiation and function during development, such as Nerve Growth Factor (NGF). NGF is essential for proper development of sympathetic and neural crest-derived sensory neurons of the peripheral nervous system as well as of central cholinergic neurons. In previous studies, using a maternal separation paradigm, we have shown that NGF expression is increased in the dentate gyrus and the hilus of the hippocampus as a result of brief (45 min) maternal separations. In the present study neonatal rats were separated for longer periods of time (up to 3 h) and at different ages during development (9 and 16 days postnatally). Results indicate that the effects of maternal separation on NGF expression are stronger with longer separations and are not restricted to the hippocampal region but can be seen also in other brain areas. Overall these results indicate that external factors, such as the presence/absence of the mother, can modify neurotrophic factor's availability in the brain, thus indicating NGF as a potential player in environmentally-mediated brain plasticity during development.

Animals↗
PubMed2000

Neurobehavioural effects of hypergravity conditions in the adult mouse.

To evaluate the behavioural response to a hypergravity condition in CD-1 mice, young adult subjects of both sexes were exposed to 2 g for a single 60 min rotational session. Motion sickness (MS) and ethological-type scoring of different activities were used to evaluate the behavioural response. Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) levels were also assessed. Behavioural scores indicated a transient mild sickness associated with hypergravity, with reduction in spontaneous activity. In males kaolin consumption (a MS index) increased following rotation while females consumed more kaolin irrespective of whether they have been rotated or simply exposed to the noise and vibration of the rotational apparatus. In males, hypothalamic NGF levels were markedly increased after rotation while no major changes were observed in central BDNF expression. These results indicate mice may represent a suitable MS model.

Animals↗
PubMed2000

Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration.

The antipsychotics haloperidol and risperidone are widely used in the therapy of schizophrenia. The former drug mainly acts on the dopamine (DA) D(2) receptor whereas risperidone binds to both DA and serotonin (5HT) receptors, particularly in the neurons of striatal and limbic structures. Recent evidence suggests that neurotrophins might also be involved in antipsychotic action in the central nervous system (CNS). We have previously reported that haloperidol and risperidone significantly affect brain nerve growth factor (NGF) level suggesting that these drugs influence the turnover of endogenous growth factors. Brain-derived neurotrophic factor (BDNF) supports survival and differentiation of developing and mature brain DA neurons. We hypothesized that treatments with haloperidol or risperidone will affect synthesis/release of brain BDNF and tested this hypothesis by measuring BDNF and TrkB in rat brain regions after a 29-day-treatment with haloperidol or risperidone added to chow. Drug treatments had no effects on weight of brain regions. Chronic administration of these drugs, however, altered BDNF synthesis or release and expression of TrkB-immunoreactivity within the brain. Both haloperidol and risperidone significantly decreased BDNF concentrations in frontal cortex, occipital cortex and hippocampus and decreased or increased TrkB receptors in selected brain structures. Because BDNF can act on a variety of CNS neurons, it is reasonable to hypothesize that alteration of brain level of this neurotrophin could constitute one of the mechanisms of action of antipsychotic drugs. These observations also support the possibility that neurotrophic factors play a role in altered brain function in schizophrenic disorders.

Animals↗
PubMed2000

Nerve growth factor antibody exacerbates neuropathological signs of experimental allergic encephalomyelitis in adult lewis rats.

In this study, experimental allergic encephalomyelitis (EAE) rats and rats exhibiting EAE expressing high circulating anti-nerve growth factor antibody were daily monitored for clinical signs and chronic relapses. Eighty-five days after EAE induction, blood, spinal cord and brain stem were used for histological examination, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) evaluation. The results showed that NGF-deprived rats display more severe clinical signs of disease. These effects were associated with a significant reduction of NGF in the brain stem and spinal cord but not of BDNF, which decreased only in spinal cord. These observations provide additional support to the hypothesis of a protective NGF role in rats exhibiting EAE.

Acute Disease↗
PubMed2000

Mapping the differences in the brain concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression.

Antidepressant drugs as well as electroconvulsive stimuli can significantly influence brain concentrations of neurotrophic factors. However, it is not known whether the baseline brain concentrations of neurotrophic factors are altered in human subjects suffering from affective disorders or whether there are sex differences in concentrations of neurotrophins in human brain. In order to elucidate some of these questions, we measured by ELISA brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls, the Flinders Resistant Line (FRL). Altered BDNF and NGF concentrations were found in frontal cortex, occipital cortex, and hypothalamus of depressed FSL compared to FRL control rats. Furthermore, different levels of these neurotrophins were also found in the male and female brain. Cumulatively these observations suggest that BDNF and NGF may play a role in depression and, hypothetically, different brain regional concentrations of BDNF and NGF in male and female animals may be relevant to gender differences in vulnerability to depression.

Animals↗
PubMed2000

Further evidence for a role of nitric oxide in experimental allergic encephalomyelitis: aminoguanidine treatment modifies its clinical evolution.

The role of nitric oxide (NO) in inflammatory/demyelinating diseases is undergoing extensive investigation as a potential target for therapeutic intervention. However, interference with NO production has resulted in contrasting effects on the development of experimental allergic encephalomyelitis (EAE), the most widely used experimental model for multiple sclerosis (MS). Purpose of this paper was both the analysis of the individual clinical evolution of EAE induced in Lewis female rats by active immunisation and the evaluation of the effect of treatment with aminoguanidine, a selective inhibitor for the inducible isoform of nitric oxide synthase (iNOS). In our experimental model, relapse occurred in 66% of animals. Aminoguanidine treatment, started 3 days before immunisation, guaranteed a complete recovery from the acute phase and a delayed, milder relapse. Moreover, 79 days after immunisation inflammatory cellular infiltrates in the spinal cord were reduced. These data further support the involvement of NO in EAE evolution.

Acute Disease↗
PubMed2000

Topical treatment with nerve growth factor for neurotrophic keratitis.

OBJECTIVE: To evaluate the efficacy of nerve growth factor (NGF) in patients with neurotrophic keratitis. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Forty-five eyes of 43 consecutive patients with moderate (stage 2, n = 17) to severe (stage 3, n = 28) neurotrophic keratitis unresponsive to other nonsurgical therapies. METHODS: After a 10-day washout with preservative-free artificial tears, 45 eyes with neurotrophic keratitis received murine NGF (200 microg/ml) every 2 hours for 2 days followed by one drop six times daily until the ulcer healed. A maintenance dose of one drop NGF (100 microg/ml) was administered four times daily for the 2 weeks subsequent to ulcer healing. MAIN OUTCOME MEASURES: Size and depth of the ulcer or the epithelial defect, corneal sensitivity, best corrected visual acuity, side effects, and relapse of the disease in the follow-up period. RESULTS: All patients had a complete resolution of the persistent epithelial defect (with or without an ulcer) after 12 days to 6 weeks of treatment with NGF. Patients affected by both stages of the disease demonstrated both improved corneal sensitivity and visual acuity (P<0.001). No significant differences were observed in the time to complete corneal healing between stage 2 and stage 3 patients. Hyperemia and ocular and periocular pain were side effects reported during the first days of treatment. No relapse of the disease was observed during the follow-up period, with the exception of three patients with trigeminal nerve resection, who required a single retreatment. CONCLUSIONS: Nerve growth factor eye drops improved corneal sensitivity and promoted corneal epithelial healing in both moderate and severe neurotrophic keratitis. Although performed in an uncontrolled and nonrandomized series of patients, this therapy shows promise for the restoration of ocular surface integrity and visual function in neurotrophic corneal disease.

Administration, Topical↗
PubMed2000

Learning performances, brain NGF distribution and NPY levels in transgenic mice expressing TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine involved in a variety of neurobiological activities including changing behavior and regulation of both neurotrophin and neuropeptide levels. In this study we used two lines of transgenic mice overexpressing brain TNF-alpha characterized by neurological deficits (line Tg6074) or phenotypically normal (line TgK3). We analyzed whether or not impairments in learning and memory processes due to TNF-alpha overexpression were associated with changes in endogenous brain NGF, NPY and beta-amyloid. The results indicate that full TNF-alpha transgene expression disrupted the learning capabilities of transgenic mice (both Tg6074 and TgK3). NGF decreased in the hippocampus of both transgenic mice whereas hippocampal NPY slightly potentiated in Tg6074. The decrease in NGF is correlated with deficits in spatial learning and memory whereas inflammation in the brain of Tg6074 could be responsible of the hippocampal increase in NPY. As a whole, these results show that transgenic mice overexpressing TNF-alpha in the brain represent a useful model for studying neuronal degeneration and brain inflammatory processes.

Amyloid beta-Peptides↗
PubMed2000

Increased pulmonary epithelial permeability in systemic sclerosis is associated with enhanced cutaneous nerve growth factor expression.

Background: Nerve growth factor (NGF), a neurotrophic factor that indirectly induces fibroblast proliferation and collagen production, has been found to be increased in the affected dermis of patients with systemic sclerosis (SSc). To investigate the possibility of a relationship between cutaneous NGF production and pulmonary damage in SSc, we studied seven non-smoking scleroderma patients. Methods: Abnormalities in lung structure were assessed by radiological lung examination, and pulmonary epithelial permeability (PEP) was determined by ventilation lung scintigraphy. All patients underwent skin punch biopsy with NGF immunohistological staining. Results: A statistically significant correlation was found between the PEP values and the cutaneous NGF staining scores, which were markedly increased in all of the patients examined, irrespective of the age, disease duration, or radiologically defined lung abnormalities. Conclusion: These results support the hypothesis that functional and anatomical changes in SSc target organs may be determined by a local tissue hyperproduction of NGF.

Journal Article↗
PubMed2000

Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome.

The neurotrophin nerve growth factor (NGF) is a major regulator of peripheral and central nervous system development. Serum NGF was measured in normally developing control children (n=26) and in individuals affected by congenital syndromes associated with learning disability: either Williams syndrome (WS; n=12) or Down syndrome (DS; n=21). Participants were assessed at three distinct developmental stages: early childhood (2 to 6 years), childhood (8 to 12 years), and adolescence (14 to 20 years). A sample was taken only once from each individual. Serum NGF levels were markedly higher in participants with WS, than DS and control participants. In addition, different developmental profiles emerged in the three groups: while in normally developing individuals NGF levels were higher in early childhood than later on, children with WS showed constantly elevated NGF levels. When compared to control participants, those with DS showed lower NGF levels only during early childhood. Neuropsychological assessment confirmed previously reported differences among the three groups in the development of linguistic/cognitive abilities. Some features of individuals with WS, such as hyperacusis and hypertension, could be related to high-circulating NGF levels.

Adolescent↗
PubMed2000

Cholecystokinin-8 enhances nerve growth factor synthesis and promotes recovery of capsaicin-induced sensory deficit.

Alterations of nerve growth factor (NGF) expression have been demonstrated during peripheral nerve disease and the impaired expression or synthesis and transportation of NGF has been correlated with the pathogenesis of several peripheral neuropathies. Since exogenous NGF administration seems to cause undesired side-effects, therapeutical strategies based on the regulation of endogenous synthesis of NGF could prove useful in the clinical treatment of these disorders. The aim of the present study was to analyse the effects of exogenous peripheral administration of the neuropeptide cholecystokinin-8 (CCK-8) on endogenous NGF synthesis, NGF mRNA and distribution of peripheral neuropeptides which are known to be regulated by this neurotrophin. To address these questions we studied the effects of capsaicin (CAPS) before and after the administration of CCK-8 on NGF levels, NGF mRNA expression and localization, and the concentration of substance P (SP) and calcitonin gene-related peptide (CGRP) in peripheral tissue These studies demonstrate that administration of the CCK-8 induces an increase of NGF protein and mRNA in peripheral tissue. NGF level in paw skin of CAPS/CCK-8-treated mice is 3 fold higher than in controls (1241+/-110 pg gr(-1) of tissue wet weight versus 414+/-110 pg gr(-1) of controls) and nearly 6 fold higher than in CAPS-treated mice (1241+/-110 pg gr(-1) versus 248+/-27 pg gr(-1)). The increase of NGF is correlated with the recovery of impaired nocifensive behaviour and with an overexpression of SP and CGRP. The evidence that CCK-8 promotes the recovery of sensory deficits suggests a potential clinical use for this neuropeptide in peripheral neuropathies.

Animals↗
PubMed2000

Peritonectomy and hyperthermic antiblastic perfusion in the treatment of peritoneal carcinomatosis.

AIMS: Some low-grade malignant tumours arising in the abdomen tend to remain loco-regionally confined to peritoneal surfaces, without systemic dissemination. In these cases complete surgical tumour cytoreduction followed by intra- or post-operative regional chemotherapy has curative potential. The aim of this study was to evaluate the outcome for patients treated in this way. METHODS: Peritonectomy was performed, involving the complete removal of all the visceral and parietal peritoneum involved by disease. After peritonectomy, hyperthermic antiblastic perfusion was carried out throughout the abdominopelvic cavity for 90 min, at a temperature of 41.5-42.5 degrees C, with mitomycin C (3.3 mg/m2/l) and cisplatin (25 mg/m2/l) (for appendicular or colorectal primaries), or cisplatin alone (for ovarian primaries). Alternatively, the immediate post-operative regional chemotherapy was performed with 5-fluorouracil (13.5 mg/kg) and Lederfolin (125 mg/m2) (for colonic or appendicular tumours) or cisplatin (25 mg/m2) (for ovarian tumours), each day for 5 days. RESULTS: Thirty-five patients affected by extensive peritoneal carcinomatosis were submitted to peritonectomy, with no residual macroscopic disease in all cases except three. Twenty-six patients were able to undergo the combined treatment involving loco-regional chemotherapy. Complications were observed in 54% of the patients and led to death in four of them. At a mean follow-up of 17 months overall 2-year survival was 55.2%, with a median survival of 26 months. CONCLUSIONS: After a learning curve of 18 months the feasibility of the integrated treatment increased to more than 90%, while mortality decreased dramatically. The curative potential of the combined therapeutic approach seems high in selected patients with peritoneal carcinomatosis not responding to systemic chemotherapy. Careful selection of patients can minimize the surgical risk, but the treatment should currently be reserved for clinical trials.

Adult↗