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Biomedical subjects

M Brunelli

Publications and source records attributed to M Brunelli.

At least 19 recordsLinked to original sources
PubMed2006

Acetyl-L-carnitine affects nonassociative learning processes in the leech Hirudo medicinalis.

Acetyl-L-carnitine is a natural molecule widely distributed in vertebrate and invertebrate nervous system. It is known to have significant effects on neuronal activity playing a role as neuroprotective and anti-nociceptive agent, as well as neuromodulatory factor. About its capability of affecting learning processes the available data are controversial. In the present study, we utilized the simplified model system of the leech Hirudo medicinalis to analyze the effects of acetyl-L-carnitine, assessing whether and how it might affect elementary forms of nonassociative learning processes. In leeches with the head ganglion disconnected from the first segmental ganglion, repetitive application of weak electrical shocks onto the caudal portion of the body wall induces habituation of swim induction whereas brush strokes on the dorsal skin produces sensitization or dishabituation when the nociceptive stimulus is delivered on previously habituated animals. Herein, the effects of different concentrations of acetyl-L-carnitine (2 mM - 0.05 mM) have been tested at different times on both sensitization and dishabituation. The results show that a single treatment of acetyl-L-carnitine blocked the onset of sensitization in a dose- and time-dependent manner. In fact, the most effective concentration able to block this process was 2 mM, which induced its major effects 11 days after the treatment, whereas 0.05 mM was unable to affect the sensitization process at all considered time points. On the contrary, acetyl-L-carnitine did not completely abolish dishabituation at the tested concentrations and at every time point. Finally, acetyl-L-carnitine also impaired the habituation of swim induction, but only 11 days after treatment.

Acetylcarnitine↗
PubMed2004

Acetyl-L-carnitine induces a sustained potentiation of the afterhyperpolarization.

Acetyl-L-carnitine is known to improve many aspects of the neural activity even if its exact role in neurotransmission is still unknown. This study investigates the effects of acetyl-L-carnitine in T segmental sensory neurons of the leech Hirudo medicinalis. These neurons are involved in some forms of neural plasticity associated with learning processes. Their physiological firing is accompanied by a large afterhyperpolarization that is mainly due to the Na+/K+ ATPase activity and partially to a Ca2+ -dependent K+ current. A clear-cut hyperpolarization and a significant increase of the afterhyperpolarization have been recorded in T neurons of leeches injected with 2 mM acetyl-L-carnitine some days before. Acute treatments of 50 microM acetyl-L-carnitine induced similar effects in T cells of naive animals. In the presence of apamin, a pharmacological blocker of Ca2+ -dependent K+ channel, acetyl-L-carnitine still enhanced the residual afterhyperpolarization, suggesting an effect of the drug on the Na+/K+ATPase. Acetyl-L-carnitine also increased the hyperpolarization induced by intracellular injection of Na+ ions. Therefore, acetyl-L-carnitine seems to be able to exert a positive sustained effect on the Na+/K+ ATPase activity in leech T sensory neurons. Moreover, in these cells, widely arborized, the afterhyperpolarization seems to play an important role in determining the action potential transmission at neuritic bifurcations. A computational model of a T cell has been previously developed considering detailed data for geometry and the modulation of the pump current. Herein, we showed that to a larger afterhyperpolarization, due to the acetyl-L-carnitine-induced effects, corresponds a decrement in the number of action potentials reaching synaptic terminals.

Acetylcarnitine↗
PubMed2003

Static and dynamic water molecules in Cu,Zn superoxide dismutase.

Understanding protein hydration is a crucial, and often underestimated issue, in unraveling protein function. Molecular dynamics (MD) computer simulation can provide a microscopic description of the water behavior. We have applied such a simulative approach to dimeric Photobacterium leiognathi Cu,Zn superoxide dismutase, comparing the water molecule sites determined using 1.0 ns MD simulation with those detected by X-ray crystallography. Of the water molecules detected by the two techniques, 20% fall at common sites. These are evenly distributed over the protein surface and located around crevices, which represent the preferred hydration sites. The water mean residence time, estimated by means of a survival probability function on a given protein hydration shell, is relatively short and increases for low accessibility sites constituted by polar atoms. Water molecules trapped in the dimeric protein intersubunit cavity, as identified in the crystal structure, display a trajectory mainly confined within the cavity. The simulation shows that these water molecules are characterized by relatively short residence times, because they continuously change from one site to another within the cavity, thus hinting at the absence of any relationship between spatial and temporal order for solvent molecules in proximity of protein surface.

Algorithms↗
PubMed2003

The transient depression of hippocampal CA1 LTP induced by chronic intermittent ethanol exposure is associated with an inhibition of the MAP kinase pathway.

Using electrophysiological and biochemical approaches, we investigated the effects of chronic, intermittent ethanol (CIE) treatment on activation of the mitogen activated protein kinase (MAPK), also known as extracellular signal regulated protein kinase 1 and 2. In hippocampal slices taken from control rats, brief high-frequency stimulation to Schaffer collateral fibers induced a large post-tetanic potentiation (PTP) in the CA1 region that decayed to stable long-term potentiation (LTP) of field extracellular postsynaptic potentials. Western blot analyses showed that phosphorylation of MAPK was increased during PTP and returned to baseline levels during LTP. In slices from the rats removed immediately from CIE treatment, PTP and MAPK activation during the PTP was significantly less than that observed in control slices and LTP was absent. In slices from rats subjected to 1 day withdrawal from CIE treatment, both the reduction in MAPK phosphorylation during PTP and the impairment of PTP and LTP were still evident. Recovery of PTP and partial recovery of LTP was observed in slices obtained from 5-day withdrawn rats. However, MAPK activation during PTP was still attenuated significantly. Interestingly, MAPK activation was enhanced significantly during LTP in 5-day withdrawn rats as well as the sensitivity to MAPK inhibitor PD 098059. In addition to these changes in HFS-induced MAPK activation, we also observed a significant reduction in the basal phosphorylation of MAPK in slices removed from rats immediately after CIE treatment. These results implicate the MAPK signal transduction pathway as a potential cellular target of ethanol. Alterations in MAPKs could play an important role in the alcohol-induced changes in synaptic plasticity associated with the effects of alcohol abuse on learning and memory processes.

Alcoholism↗
PubMed2001

Nonassociative learning in the leech Hirudo medicinalis.

In the present study we examined nonassociative learning of the induction of swimming which was evoked by weak electrical stimulation in the leech Hirudo medicinalis. The behavioural response to stimuli applied repeatedly to the body wall at an inter-trial interval (ITI) of 1 min decreased, eventually ceased, and then recovered spontaneously. More rapid reduction of the behavioural response occurred in repeated training sessions. This decrement of response conformed to the operational definition of habituation. Moreover, a noxious stimulus (i.e. brushing on the skin) facilitated the decremented response (dishabituation). In addition, we compared response decrement in naive animals with decrement in dishabituated and in sensitized animals. The analysis of the best fitting functions of the habituation, the habituation of dishabituation and the habituation of sensitization revealed interesting differences in these processes.

Animals↗
PubMed2001

Pituitary adenylate cyclase-activating polypeptide hormone (PACAP) at very low dosages improves memory in the rat.

To ascertain whether very low dosages of pituitary adenylate cyclase-activating polypeptide (PACAP) influence learning in mammals, immediately after the acquisition trial of a passive avoidance response (PAR) paradigm, PACAP-38 was administered intracerebroventricularly at increasing dosages (0, 0.02, 0.2, 2, 20, and 200 ng in 10 microl saline) to different groups of rats. The mnemonic effects were measured by means of retention testing 48 and 96 h later. At intermediate PACAP-38 concentrations there was a significant mnemonic improvement of the PAR. The maximal effect was observed after the 0.2-ng PACAP-38 administration (longer step-through latencies). There was a lesser effect at the subsequent higher concentration, 2 ng. Higher dosages had no effects. It is concluded that PACAP-38 acts as an enhancer of mammalian mnemonic processes even at very low dosages. The positive effect follows an inverted U-shaped dose-response curve. The results may be of interest for the therapy of some neuropathological conditions.

Animals↗
PubMed2001

Caulerpenyne, a toxin from the seaweed Caulerpa taxifolia, depresses afterhyperpolarization in invertebrate neurons.

The massive invasion of the Mediterranean Sea by the tropical seaweed Caulerpa taxifolia (Vahl) C. Agardh has stimulated several investigations in order to test the environmental risk from an ecotoxicological point of view. The studies carried out on various experimental models have shown that caulerpenyne, the major metabolite synthesized by the seaweed, affects several cellular and molecular targets. In addition, neurological disorders have been reported in patients who accidentally ate C. taxifolia, but no evidence about the potential effects of the seaweed and of its metabolites on nerve cells were up to now available. Herein we describe that caulerpenyne modifies the electrical properties of touch mechanosensory cells of the leech Hirudo medicinalis. The physiological firing of these cells causes an afterhyperpolarization that is mainly due to the activity of the Na+/K+-ATPase and to a lesser extent to a calcium-dependent potassium current. Caulerpenyne depressed this afterhyperpolarization; the effect was dose-dependent and partially reversible. Experiments have been carried out in order to understand the mechanism through which caulerpenyne reduced the afterhyperpolarization. The action of the biotoxin has been tested in the presence of pharmacological blockers of calcium-dependent potassium channels such as cadmium and apamin. In these experimental conditions, caulerpenyne still reduced the residual afterhyperpolarization, suggesting a direct effect of the toxin on the Na+/K+-ATPase. In order to test this hypothesis, we have performed experiments where the Na+/K+-ATPase was activated by the intracellular injection of sodium and where also its basal activity was modified as well. From the data collected we suggest that caulerpenyne inhibits both the basal and the sodium-induced activity of the Na+/K+-ATPase in leech touch neurons.

Animals↗
PubMed2001

Adult primary teratoma of the testis--report on 5 cases in clinical stage I disease.

OBJECTIVES: Testis pure teratoma accounts for 2.7% to 3% of all germ cell tumors in adult where it behaves as a malignant neoplasm. Pure teratoma of the testis presents in clinical stage I disease in 44% of the patients whose risk of having pathological stage II disease is 16.7% to 19.2%. Herein we report on 5 cases of adult pure teratoma of the testis presenting itself in clinical stage I disease. MATERIALS AND METHODS: From September 1976 to February 2000, 75 patients underwent orchidectomy for clinical stage I nonseminomatous germ cell cancer of the testis. Testis pure teratoma was detected in 5 patients (7%). Testis tumor markers were evaluated in all cases. Patients underwent imaging examination to detect the clinical stage of the disease. Treatment options after orchidectomy included retroperitoneal lymph node dissection (RPLND) in 4 patients and surveillance in 1. RESULTS: The average age of the patients was 31 years (range 24-45). The tumor was on the left sided in 3 cases (60%) and right in 2 (40%). Tumor average size was 3.2 cm (rang 1-6). Histopathology detected the following subtypes: mature teratoma in 3 cases (60%), immature teratoma in 1 (20%) and teratoma with malignant transformation in (20%). All patients were at clinical stage I disease. Germ cell cancer microscopic metastatic disease including embryonal carcinoma was detected in I dissected lymph node of 1/4 patients (25%). Average follow up was 166 months (range 93-249). All patients were alive and disease free and no relapses were detected during the follow up period. CONCLUSIONS: Primary pure teratoma of the testis does not respond to chemotherapy nor does it to radiation therapy. The disease treatment options after orchidectomy for patients with clinical stage I disease include RPLND or surveillance with their relative risks and benefits. RPLND is the chosen treatment because it is both staging and treating. A close a long term follow up is required since pure teratoma metastatic disease may clinically develop after more than 10 years.

Adult↗
PubMed2001

Adrenal extramedullary hematopoiesis: report on a pediatric case and update of the literature.

The authors report on a rare pediatric case of adrenal extramedullary hematopoiesis in a patient with beta-thalassemia disease. The lesion was clinically discovered as incidentaloma of the right adrenal gland and treated by surgery. Adrenal extramedullary hematopoiesis may clinically be detected as incidentaloma. Adrenal incidentalomas presenting with hematologic disorders, such as agnogenic myeloid aplasia and beta-thalassemia, need careful imaging as well as adrenal hormonal investigation in order to exclude malignancy and subclinical hypersecretory syndromes. Ultrasound or CT-FNA of the lesion are effective in finding out the disease.

Adrenal Gland Neoplasms↗
PubMed2001

Parvalbumin is constantly expressed in chromophobe renal carcinoma.

Chromophobe renal carcinoma is composed of neoplastic cell showing several features similar to those found in the intercalated cells of the collecting ducts. Because the distal nephron expresses calcium-binding proteins playing a role in calcium homeostasis, we reasoned that these proteins could be expressed by chromophobe carcinoma and therefore represent a diagnostic marker. We studied the immunohistochemical expression of different calcium-binding proteins (parvalbumin, calbindin-D28K, and calretinin) in 140 renal tumors, including 75 conventional (clear cell) carcinomas, 32 chromophobe carcinomas, 17 papillary renal cell carcinomas, and 16 oncocytomas. Parvalbumin was strongly positive in all primary chromophobe carcinomas and in one pancreatic metastasis; it was positive in 11 of 16 oncocytomas and absent in conventional (clear cell) and papillary renal cell carcinomas, either primary or metastatic. Calbindin-D28K and calretinin were negative in all tumors, with the exception of two chromophobe carcinomas, four oncocytomas, and two papillary renal cell carcinomas showing inconspicuous calretinin expression. Our data demonstrate that parvalbumin may be a suitable marker for distinguishing primary and metastatic chromophobe carcinoma from conventional (clear cell) and papillary renal cell carcinoma. Moreover, they suggest a relationship between chromophobe renal carcinoma and renal oncocytoma and indicate that chromophobe carcinoma exhibits differentiation toward the collecting-duct phenotype.

Calbindin 1↗
PubMed2001

Long-lasting hippocampal potentiation and contextual memory consolidation.

In order to ascertain whether there are hippocampal electrophysiological modifications specifically related to memory, exploratory activity and emotional stress, extracellular electrical activity was recorded in hippocampal slices prepared from the brains of male adult rats. Several groups of animals were employed: (i) rats which had freely explored the experimental apparatus (8 min exposure); (ii) rats which had been subjected, in the same apparatus, to a fear conditioning paradigm training entailing the administration of aversive electrical footshocks (8 min exposure); (iii) rats to which the same number of aversive shocks had been administered in the same apparatus, but temporally compressed so as to make difficult the association between painful stimuli and the apparatus (30 s exposure); (iv) naïve rats never placed in the apparatus. Half of the rats from each treatment group were used for retrieval testing and the other half for hippocampal excitability testing. The conditioned freezing response was exhibited for no less than 4 weeks. Hippocampal excitability was measured by means of input-output curves (IOC) and paired-pulse facilitation curves (PPF). Retrieval testing or brain slices preparation were performed at increasing delays after the training sessions: immediately afterwards or after 1, 7 or 28 days. Only the rats subjected to the fear conditioning training exhibited freezing when placed again in the apparatus (retrieval testing). It was found that IOCs, with respect to naïve rats, increased in the conditioned animals up to the 7-day delay. In free exploration animals the IOCs increased only immediately after the training session. In all other rats no modification of the curves was observed. IOC increases do not appear to imply presynaptic transmitter release modifications, because they were not accompanied by PPF modifications. In conclusion, a clear-cut correlation was found between the increase in excitability of the Schaffer collateral-CA1 dendrite synapses and freezing response consolidation.

Animals↗
PubMed2001

Primary lymphoma of the epididymis: case report and review of the literature.

OBJECTIVE: To report an extremely rare clinical pathological observation of a case of primary lymphoma of the epididymis, without testicular or systemic involvement, and to update the relevant literature. MATERIALS AND METHODS: A 25-year-old white male patient complaining of right scrotal pain was referred to our department. Clinical examination detected a hard painful mass at the right epididymal head. Epididymitis was diagnosed and conservative therapy with antibiotics and anti-inflammatory drugs was given. After 2 months of therapy the patient was admitted to our department because a tumor was suspected. Tumor markers were normal. Right scrotal exploration was performed through a standard inguinal incision. The epididymal head was completely replaced by a hard white mass. Fresh frozen sections indicated a malignant tumor. Right radical orchiectomy was performed. RESULTS: High-grade primary epididymal non-Hodgkin's lymphoma with diffuse large cells (group G according to the Working Formulation) was diagnosed. Clinical pathological staging detected stage IE (extranodal) primary epididymal lymphoma. The patient was referred to the Hematologic Unit for combined chemotherapy, according to the VACOP-B protocol. After an 18-month follow-up the patient is well and disease free. CONCLUSIONS: When an epididymal mass does not benefit from medical treatment, scrotal exploration and fresh frozen sections of the lesion should be done. The possible bilateral involvement by primary epididymal lymphoma has to be kept in mind. Radical orchiectomy is the treatment of choice for primary lymphoma of the epididymis. Adjuvant chemotherapy is indicated in high-grade malignant lymphoma. Prognostic parameters of the disease may be the grade of malignancy and the size of the tumor.

Adult↗
PubMed2000

Neurotoxic effects of caulerpenyne.

1. In this paper the authors tested the effect of caulerpenyne (CYN), a sesquiterpene synthesized by the green alga Caulerpa taxifolia onto the central nervous system of the leech Hirudo medicinalis. Investigations have been performed with three different approaches: neuroethological, electrophysiological and neurochemical techniques. 2. CYN application mimics the effect of a nociceptive stimulation (brushing), eliciting a clear-cut potentiation of the animal swim response to the test stimulus (non associative learning process such as sensitization). This effect is similar to that one induced by the endogenous neurotransmitter serotonin (5HT). 3. CYN strongly reduces the after-hyperpolarization (AHP) recorded from T sensory neurons. This effect overlaps that one produced by 5HT, but it is not affected by the serotonergic antagonist methysergide. 4. The decrease of AHP amplitude due to CYN application is observed also in presence of apamin, a blocking agent of Ca++-dependent K+ channels, suggesting that CYN is acting through the inhibition of the Na+/K+ electrogenic pump. 5. The depression of the AHP driven by CYN is not prevented by application of MDL 12330A, an adenylate cyclase inhibitor. On the other hand MDL 12330A counteracts the reduction of AHP due to 5HT application. 6. Incubation of the leech central nervous system with CYN induces the phosphorylation of proteins of 29, 50, 66 and 100 kDa. This pattern of phosphorylation is similar to that one elicited by 5HT treatment. 7. The data demonstrate that CYN exerts remarkable effects on leech neurons by acting onto specific molecular targets such as the Na+/K+ ATPase. This effect may influence important neural integrative functions and may explain the sensitizing action produced by the toxin on swim induction. Finally, caulerpenyne does not act through the pathways involved in the 5HT action, and its effect is not mediated by the second messenger cyclic AMP. The mechanism of action of CYN are still under investigations.

Animals↗
PubMed1997

Neurobiological principles of learning and memory.

An increasing flow of evidences collected on elementary forms of learning processes in selected animal models evidentiates some mechanisms which can represent the basic cellular principles underlying plastic changes: 1. 5HT and second messengers of nucleotide type (like cAMP) have a pivotal role in the learning process. 2. In almost all short-term learning processes the modifications are subserved by a mechanism of protein phosphorylation. 3. In various animal models the modulation of K+ and Ca2+ channels is the molecular mechanism for learning. Experiments performed in sensory T neuron of the leech indicate that the modulation of Na+/K+ electrogenic pump is one of the fundamental mechanism for learning. 4. In long-term plastic changes, the most important finding is that newly synthesized proteins are formed. 5. In addition to what has been observed in the Aplysia model, where changes in synaptic efficacy represent the basic principles of memory storage, in the leech it has been demonstrated that a molecular machinery present in a single neuron can adapt the activity of the cell to environmental stimuli.

Amnesia↗
PubMed1997

[Genetics of laryngeal cancer: an experimental study].

Squamous cell laryngeal carcinoma accounts for 1% of all cancer deaths and 95% of all laryngeal malignancies. It is most frequently found in smokers over 40 years of age. This neoplasm is presently the object of cytogenetic studies in an attempt to identify a specific chromosome pattern. In a study of 29 cases of malignant primary laryngeal tumor, Nawroz (1993) found a loss of alleles in different loci mapped in the short arm of chromosome 9 (9p) in more than two-thirds of the cases. In the same chromosome region, the loss of heterozygotes (LOH) was previously described in other neoplasms (leukemia, hematic tumors, melanomas). In an attempt to verify the predominant chromosome pattern and the loss of heterozygotes in chromosome 9, a cytogenetic, genetic-molecular study was performed on ten cases of laryngeal carcinoma. Among these subjects, two showed a hyperdiploid chromosome pattern (metaphase with more than 46 chromosomes per cell), five had a hypodiploid pattern (with less than 46 chromosomes per cell) while, for the remaining three cases, it was not possible to identify any metaphase. Numerous structural and numerical karyotype defects were found in chromosomes 1, 3, 4, 5, 9, 10, 13, 14, 16, 18, and Y. In 6 of the cases abnormality was found in chromosome 9 while in 10 it was apparently a homozygote. The study was performed with the use of fluorescent in situ hybridization (FISH) using a chromosome library specific for chromosome 9. A loss of the 9p segment could be found as a result of different types of alterations: deletion (case 1, 2, 5, 7); non uniform transfer between chromosome 2 and chromosome 9 (case 2); other transfers involving the 9p segment (case 1, 4, 5, 7, 10). In six cases, analysis was further detailed at the molecular level by means of DNA amplification methods (PCR) and electrophoresis on denatured 10% polyacrylammide gels. LOH was studied using a polymorphic system specific for the short arm of chromosome 9. Four of the cases examined showed LOH for the system used while one case (case 4) gave no information. Case 9 did not show any loss of alleles. The present study suggests that the loss of a DNA sequence on chromosome 9p is primary to the neoplastic progression in laryngeal cancer.

Aged↗
PubMed1996

Age-Specific Anti-Hepatitis A Virus Seroepidemiology in Italian Travelers: Indications for Anti-Hepatitis A Vaccination.

Background: Hepatitis A virus (HAV) circulation in the environment is decreasing in most industrialized Western countries. This decrease has lead to low seroprevalence rates in adults. As a consequence, many nonimmune unprotected travelers from areas of low prevalence are considered at risk of acquiring HAV infection when traveling to high HAV endemic areas in developing countries. The recent HAV inactivated vaccine has proved safe and effective, and its use in different geographic areas should be guided by local age-specific HAV seroprevalence rates. The aim of this paper is to describe the age-specific sero-epidemiology of HAV infection in travelers from a highly industrialized region in Northern Italy (Lombardy). Methods: Seven hundred and forty-four consecutive travelers aged from 20 to 59 years, subdivided in 10-year age groups, gave blood samples in the collaborative Health Centers in the Lombardy region and sera were tested for HAV IgG antibodies. A questionnaire was given to travelers that investigated alimentary habits and a history of previous travel. Results: Anti-HAV seroprevalence was 18.0%, 58.0%, 75.8%, and 89.5% in the 20-29, 30-39, 40-49, and 50-59 age groups, respectively. Age was the single most important determinant of anti-HAV seroprevalence. The influence of previous travels, eating shellfish, or ingestion of self-cultivated vegetables was ruled out by multivariate analysis. Conclusions: In the Lombardy region (Northern Italy), age specific anti-HAV seroprevalence rates are much higher than those reported in other Western European countries. The cost-benefit analysis suggested that travelers born after 1960 do not need serologic screening before vaccination. Whenever possible, however, HAV serologic screening is advisable for travelers born before 1960. However, the severity of the disease in older subjects, and the proved safety of HAV vaccination in immune subjects, may advise d'emblée HAV vaccination without prior screening, when serologic investigation is unfeasible because of lack of time or the unavailability of testing facilities.

Journal Article↗