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Biomedical subjects

A Rossi

Publications and source records attributed to A Rossi.

At least 343 records · Page 19Linked to original sources
PubMed1997

Inhibition of nuclear factor kappa B by prostaglandin A1: an effect associated with heat shock transcription factor activation.

Prostaglandins (PGs) function as intracellular signal mediators in the regulation of a variety of physiological and pathological processes, including inflammation and immune responses. Cyclopentenone PGs are characterized by antiviral activity against several viruses, including human immunodeficiency virus type 1 (HIV-1), and by the ability to induce heat shock protein expression through activation of the heat shock transcription factor. Here we report that PGA1 is a potent inhibitor of nuclear factor-kappa B (NF-kappa B) activation in human cells and of NF-kappa B-dependent HIV-1 transcription in long terminal repeat-chloramphenicol acetyl-transferase transient transfection experiments. PGA1 acts by inhibiting phosphorylation and preventing degradation of the NF-kappa B inhibitor I kappa B-alpha. Inhibition does not require protein synthesis, is dependent on the presence of a reactive cyclopentenonic moiety, and is associated with heat shock transcription factor activation. Because NF-kappa B is critically involved in the activation of immunoregulatory and viral genes, inhibition of its activity could be a major component of the immunosuppressive and antiviral activity of PGs.

Cycloheximide↗
PubMed1997

Maximal inspiratory pressure and inspiratory muscle endurance time in asthmatic children: reproducibility and relationship with pulmonary function tests.

Respiratory muscle strength, assessed by maximal inspiratory mouth pressure (PImax), and endurance, assessed as the length of time a subject could breathe against inspiratory resistance with a target mouth pressure > or = 70% of PI,max (Tlim), were measured in 20 symptomless asthmatic children, in order to assess the reproducibility of such measurements and their relationship to traditional pulmonary function tests or tests of bronchial hyperresponsiveness. After recording lung volumes and bronchial response to methacholine, PI,max and Tlim were measured twice in the same morning, with a 30-minute interval between each experimental trial. Mean (+/-SD) values of PI,max were 72.2 +/- 20.6 cmH2O in the first and 75.8 +/- 22.9 cmH2O in the second trial. Tlim was 154 +/- 65 and 164 +/- 66 seconds in the first and in the second trial respectively. A lack of agreement between different measurements was seen for both PI,max and Tlim. The coefficient of repeatability was 24.8 for PI,max and 92.3 for Tlim. A significant correlation between age and PI,max as well as between body mass index and PI,max were shown; no similar correlation was found for Tlim. No correlation was found between PI,max and Tlim in either of the two successive runs or between either PI,max or Tlim and lung volumes or bronchial response to methacholine. Our study shows that at this time the reproducibility of PI,max or Tlim in children with asthma in remission seems to be poor, although PI,max has a better reproducibility than Tlim. A standardized procedure to measure PI,max, should be obtainable in the near future. This would improve its clinical usefulness since PI,max is the only noninvasive test to assess respiratory muscle strength that can identify subjects at risk to develop respiratory muscle fatigue during an acute asthmatic attack.

Adolescent↗
PubMed1997

Energy metabolism in normal and hypertrophied right ventricle of the ferret heart.

Using an isolated ferret heart preparation (Langendorff perfusion, perfusion pressure 90 mmHg), energy metabolism has been characterized in right and left ventricles from control and hypertrophied hearts. Hypertrophy was induced by pulmonary artery clipping for 30-45 days (right ventricle wall weight/body weight ratio increased by 70%). Myocardial contents of high energy phosphate compounds, glycogen and lactate, and the activities of some enzymes were biochemically measured in perfused hearts and also after ischemic arrest (30 min global ischemia). In hypertrophied right ventricles, PCr (-46%), Cr (-34%) levels, creatine kinase activity (-18%) were significantly decreased compared with control. ATP and Pi levels were not affected by hypertrophy. The adenylate energy charges were similar (0.85-0.86) in both types of heart. The activities of hexokinase (+26%), aldolase (+212%), pyruvate kinase (+14%) and glucose 6-phosphate dehydrogenase (+107%) were increased by hypertrophy. The LDH isozyme pattern was significantly changed such that LDH3 was decreased by 11%, and LDH4 and LDH5 were increased by a factor 1.4 and 2.9 respectively in hypertrophy. After 30 min of global ischemia, PCr level was decreased by 89 and 79% in control and hypertrophied ventricles respectively. ATP level was depressed by 41 in control and only by 21% in hypertrophied muscles. Altogether, the present data suggested that, in the adult ferret heart, the capacity for the ATP synthesis could be maintained during hypertrophy by the enhancement of the glycolytic pathway. The smaller decline of ATP after ischemia in hypertrophied tissue could be explained by a lower consumption of ATP in the hypertrophied compared to the control heart during the earliest period of ischemia.

Adenosine Triphosphate↗
PubMed1997

Early alteration of the control of mitochondrial function in myocardial ischemia.

This study was aimed at evaluating the nature of the early mitochondrial alterations in isolated perfused rat hearts subjected to ischemia (37 degrees C, 0.1 ml/min, 15 or 30 min) and reperfusion (10 min). The functional variables of isolated perfused hearts were continuously evaluated, and the mitochondrial respiration variables were determined at the end of protocol on cardiac permeabilized fibers. In a parallel series of experiments, the myocardial contents of inorganic phosphate (Pi), phosphocreatine (PC) and ATP were monitored by means of P-31 NMR spectroscopy for the 15-min ischemia group. Severe mitochondrial alterations were detected in the 30-min ischemia group: decrease of maximal respiration rate and apparent Km for ADP, loss of the stimulatory effect of creatine (Cr) and disruption of the outer membrane. The functional recovery was no more than 10% of the pre-ischemic value. In contrast, in the 15-min ischemia group, only the stimulatory effect of Cr on respiration was significantly decreased. On reperfusion, a restoration of pre-ischemic levels of Pi and PC and a stabilization of the ATP content were observed, demonstrating the establishment of an energy balance steady state. The functional recovery was 76% of pre-ischemic value. We conclude that the alterations related to energy production control (by ADP and Cr) and to energy transfer are the earliest damages to mitochondrial function during ischemia. In spite of a preserved capacity for ATP production, these alterations, which persist on reperfusion, could be responsible for an altered responsiveness of the mitochondrial function to energy demand.

Adenosine Diphosphate↗
PubMed1997

Proapoptotic effect of atorvastatin on stimulated rabbit smooth muscle cells.

The in vitro and in vivo activity of atorvastatin and other 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (fluvastatin, pravastatin and simvastatin) has been investigated. Atorvastatin, fluvastatin, pravastatin and simvastatin caused a significant and dose-dependent (0.1-50 microM) reduction in cell multiplication of vascular smooth muscle cells (SMC) in cultures associated with the retardation of cycling cells in the G1 and G2/M compartments at 24 h, a phenomenon leading to apoptosis (programmed cell death) in several experimental in vitro models. The effects on the cell cycle resulted in a strong inhibition of cell proliferation at 48 h, followed by apoptosis when incubation was prolonged to 72 h as assessed by nuclei morphology and cytofluorimetric analysis of DNA. The apoptotic effect observed for the statins is completely prevented by the addition of exogenous mevalonate at a 100 microm concentration. in vivo SMC proliferation was stimulated by applying a silastic collar to the outside surface of carotid arteries in normocholesterolemic rabbits in the presence of an anatomically intact endothelium. The positioning of the collar promoted apoptosis in control vessels as assessed by Terminal Deoxynucleotidyl Transferase-dUTP-Biotin Nick-End Labeling (TUNEL) assay. The pre-treatment with 5 mg kg-1 per day of atorvastatin before collar insertion strongly increased the number of TUNEL-positive cells, suggesting a pro-apoptotic effect of HMGCoA reductase inhibitors also in vivo, even though cell DNA rearrangement still needs to be excluded. No apoptotic signal was detectable in sham operated arteries with no collar in either control or atorvastatin-treated rabbits. These data indicate that HMGCoA reductase inhibitors effect on the arterial wall may involve the modulation of both cell proliferation and programmed cell deaths supporting a possible role of statins in the prevention of early lesion and restenosis.

Animals↗
PubMed1997

Alteration in the control of mitochondrial respiration by outer mitochondrial membrane and creatine during heart preservation.

OBJECTIVE: This study aimed to evaluate the nature and extent of mitochondrial alterations during heart preservation. METHODS: Rat hearts, isolated after cardioplegia in situ, were preserved for 6 or 15 h at 4 degrees C either by immersion in cardioplegic solution or by low-flow perfusion (0.3 ml/min) with cardioplegic solution. The energy state of hearts at the end of preservation was determined by 31P-NMR spectroscopy and functional recovery was evaluated on reperfusion. Variables of mitochondrial respiration (maximal rate of respiration in the presence of ADP = delta Vmax, apparent Km for ADP, effect of creatine) were evaluated on skinned fibers and compared with those determined in controls and in hearts subjected to 1 hour of ischemia at 37 degrees C. RESULTS: Serious mitochondrial alterations were detected in fibers from 15 h immersed hearts: decrease of delta Vmax and of apparent Km for ADP, loss of the stimulatory effect of creatine, and disruption of the outer mitochondrial membrane. The extent of alternations was more accentuated in fibers from normothermic ischemic hearts, in which some damage of the inner mitochondrial membrane also occurred. In fibers from hearts preserved for 6 h, no significant changes in mitochondrial variables could be detected. When the hearts were preserved under low-flow perfusion for 15 h, only the stimulatory effect of creatine on respiration was significantly decreased. The extent of the loss of the stimulatory effect of creatine paralleled the accumulation of inorganic phosphate (Pi) during preservation and the decrease in left ventricular function on reperfusion. CONCLUSIONS: Alterations related to the outer membrane and the intermembrane space are among the earliest signs of damage to mitochondrial function during heart preservation. These alterations could be attributed to the swelling of mitochondria under the effect of Pi. The determination of mitochondrial parameters in biopsy samples could allow a simple and rapid evaluation of energy-producing and transfer capacities of the myocardium.

Adenosine Diphosphate↗
PubMed1997

The parafascicular thalamic nucleus modulates messenger RNA encoding glutamate decarboxylase 67 in rat striatum.

We investigated whether the parafascicular thalamostriatal pathway, one of the major excitatory inputs to the striatum, regulates the expression in rat striatum of messenger RNA encoding two isoforms of glutamate decarboxylase (mol. wt 67,000: glutamate decarboxylase 67 and mol. wt 65,000: glutamate decarboxylase 65). Acute (one day) and chronic (14 days) electrolytic lesions of the parafascicular nucleus resulted in 58% and 23% decreases in glutamate decarboxylase 67 messenger RNA expression, respectively, as determined by northern blot analysis. Glutamate decarboxylase 65 messenger RNA was not modified by either lesion. Sections of sham- and acute-lesioned striata were processed for in situ hybridization histochemistry at the single cell level with an RNA probe for glutamate decarboxylase 67. Labelling of glutamate decarboxylase 67 messenger RNA was decreased in both types of cells known to be present in the striatum, i.e. the lightly and the very densely-labelled neurons. The frequency distribution of glutamate decarboxylase 67 labelling per neuron in the lesioned striata, in fact, was shifted to the left and its median was lower than in the sham-lesioned striata. In view of the excitatory nature of the thalamostriatal pathway, we examined the subtype of glutamate receptors modulating the glutamate decarboxylase 67 gene expression. The N-methyl-D-aspartate-type receptor antagonist, dizocilpine, at 0.1-0.5 mg/kg i.p., produced a marked and persistent reduction in striatal glutamate decarboxylase 67 messenger RNA. The non-N-methyl-D-aspartate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (12 nmol/side, i.c.v.) had no such effect. The results provide evidence that excitatory thalamostriatal afferents selectively modulate the gene expression of glutamate decarboxylase 67, probably through the N-methyl-D-aspartate subtype of glutamate receptors.

Animals↗
PubMed1997

Determinants of pulmonary hypertension in left ventricular dysfunction.

OBJECTIVES: This study sought to analyze the determinants of pulmonary hypertension in patients with left ventricular dysfunction. BACKGROUND: Pulmonary hypertension in patients with left ventricular dysfunction is a predictor of poor outcome. The independent role of cardiac functional abnormalities in the genesis of pulmonary hypertension is unclear. METHODS: In 102 consecutive patients with primary left ventricular dysfunction (ejection fraction < 50%), systolic pulmonary artery pressure was prospectively measured by Doppler echocardiography (using tricuspid regurgitant velocity), and left ventricular systolic and diastolic function, functional mitral regurgitation, cardiac output and left atrial volume were quantified. RESULTS: Systolic pulmonary artery pressure was elevated in patients with left ventricular dysfunction (51 +/- 14 mm Hg [mean +/- SD]), but the range was wide (23 to 87 mm Hg). Of the numerous variables correlating significantly with systolic pulmonary artery pressure, the strongest were mitral deceleration time (r = -0.61, p = 0.0001; odds ratio of pulmonary pressure > or = 50 mm Hg [95% confidence interval] if < 150 ms, 48.8 [14.8 to 161]) and mitral effective regurgitant orifice (r = 0.50, p = 0.0001; odds ratio [95% confidence interval] if > or = 20 mm2, 5.9 [2.3 to 15.5]). In multivariate analysis, these two variables were the strongest predictors of systolic pulmonary artery pressure in association with age (p = 0.005). Ejection fraction or end-systolic volume was not an independent predictor of pulmonary artery pressure. CONCLUSIONS: Pulmonary hypertension is frequent and highly variable in patients with left ventricular dysfunction. It is not independently related to the degree of left ventricular systolic dysfunction but is strongly associated with diastolic dysfunction (shorter mitral deceleration time) and the degree of functional mitral regurgitation (larger effective regurgitant orifice). These results emphasize the importance of assessing diastolic function and quantifying mitral regurgitation in patients with left ventricular dysfunction.

Aged↗
PubMed1997

Spinal reflex pattern to foot nociceptive stimulation in standing humans.

Ipsi- and contralateral patterns of lower limb nociceptive reflex responses were studied in 6 normal subjects in free standing position. Once the position was stabilized, only ankle extensor muscles showed consistent tonic activity while ankle flexors and knee extensors and flexors were virtually silent. Reflex responses, elicited by painful electrical stimuli to the skin of the plantar and dorsal aspect of the foot, were recorded from ipsi- and contralateral quadriceps (Q), biceps femoris (Bic), tibialis anterior (TA) and soleus (Sol) muscles. Plantar foot stimulation evoked a large excitatory response in the ipsilateral TA at about 80 ms and a smaller responses in Bic and Q at 70 ms and 110 ms, respectively. Ipsilateral excitatory effects after dorsal foot stimulation consisted of a Bic response at about 75 ms. In addition to excitatory effects, both plantar and dorsal foot stimulation evoked long-lasting suppression of ipsilateral Sol background activity starting at about 60 ms. Contralaterally, the only nociceptive effects after plantar or dorsal foot stimulation were a small excitatory response of Sol at about 85 ms. Evidence is provided that only excitatory responses were contingent upon nociceptive volley. The main mechanical effects seen after plantar stimulation were dorsiflexion of the foot without loss of heel contact with the floor; no withdrawal response of the foot followed nociceptive dorsal stimulation. Our main conclusion is that only reflex nociceptive responses serving to avoid the stimulus without conflicting with limb support function are expressed. The mechanisms reconciling nociceptive action and postural function of the lower limbs are discussed.

Adult↗
PubMed1997

Vinorelbine is well tolerated and active in the treatment of elderly patients with advanced non-small cell lung cancer. A two-stage phase II study.

More than 30% of lung cancers arise in patients aged 70 years or more; however, because elderly patients are not considered to tolerate chemotherapy, they are generally excluded from clinical trials and are not considered eligible for aggressive cisplatin-based chemotherapy in clinical practice. The aims of the present study were to test tolerability and activity of weekly vinorelbine in advanced non-small cell lung cancer (NSCLC) patients aged 70 years or more, and to define whether minimum conditions existed for a randomised comparison with best supportive care. The study was designed as a multicentre two-stage phase II trial according to Simon's optimal design: 8 or more responses out of 43 treated patients were expected at the end of the trial. Patients aged 70 years or more were eligible if they had a cytological or histological diagnosis of NSCLC at stage IIIb-IV and a performance status less than or equal to two according to the ECOG scale. Vinorelbine was given intravenously (i.v.) at a dose of 30 mg/m2 every week for 12 doses. As planned, 43 patients entered the study; median age was 73 years (range 70-80); 11 patients were older than 75 years. Median dose-intensity (mg/m2/week) of vinorelbine was 21.2 (range 7.5-30) and was not affected by age of patients. Toxicity was generally mild, mainly haematological and never life-threatening. ECOG performance status improved in 26% of patients; cough and pain improved in more than 40% of patients symptomatic at entry, while dyspnoea improved in 28%; approximately half the patients had a stabilisation of their symptoms. 10 patients (23-95% exact confidence interval (CI): 12-39%) obtained a partial response. Median time to progression was 11 weeks (95% CI 8-30) and median survival 36 weeks (95% CI 28-53). One-year estimated progression-free and overall survival rates are 16% and 36%, respectively. In conclusion, vinorelbine was well tolerated and active in the treatment of elderly NSCLC patients. A phase III trial (ELVIS-Elderly Lung Cancer Vinorelbine Italian Study) comparing best supportive care versus best supportive care plus vinorelbine is now ongoing.

Age Factors↗
PubMed1997

[3H]ketanserin binding in human brain postmortem.

This study aimed at comparing the binding characteristics of [3H]ketanserin, a high-affinity serotonin 2A (5-HT2A) receptor antagonist, in the prefrontal cortex, hippocampus and striatum of human brain post-mortem. The results indicated the presence of a single population of binding sites in all the regions investigated, with no statistical difference in maximum binding capacity (B(max)) or dissociation constant (K(d)) values. The pharmacological profile of [3H]ketanserin binding was consistent with the labeling of the 5-HT2A receptor, since it revealed a competing drug potency ranking of ketanserin = spiperone > clozapine = haloperidol > methysergide > mesulergine > 5-HT. In conclusion, the 5-HT2A receptor, as labeled by [3H]ketanserin, would seem to consist of a homogenous population of binding sites and to be equally distributed in human prefronto-cortical, limbic and extrapyramidal structures.

Autopsy↗
PubMed1997

BEAM chemotherapy and autologous haemopoietic progenitor cell transplantation as front-line therapy for high-risk patients with diffuse large cell lymphoma.

In two consecutive and unselected cohorts of diffuse large cell lymphoma (DLCL) patients with advanced stage disease (IIB or bulk or more) and aged < 60 years, we compared a standard (MACOP-B for 12 weeks, 60 patients) versus a high-dose chemotherapy programme (8 weeks of MACOP-B plus one or two cycles of intensification with mitoxanthrone, dexamethasone, high-dose Ara-C, and finally BEAM chemotherapy with autologous haemopoietic progenitor cell transplantation, 61 patients). 41 patients (68%) in the standard group and 51 (84%) in the high-dose chemotherapy group, achieved a complete remission (CR) or an uncertain complete remission (CRu) (P = 0.0491). With a median follow-up time of 28 months for the high-dose group and 63.5 months for the standard group, the actuarial estimate of event-free survival (EFS) at 2 years demonstrates a significant benefit (70% v 50%, P = 0.03) for patients treated with the intensive regimen. The analysis of subgroups of patients showed that only high-risk patients (two or three risk factors) benefitted from the high-dose chemotherapy programme. Nevertheless, the overall survival does not show a significant difference between the two treatment modalities. The treatment-related morbidity was similar and the mortality rate was 8% in the standard (MACOP-B) group and 3% in the high-dose chemotherapy programme. In conclusion, our results show that high-dose chemotherapy and autologous stem cell transplantation is a safe procedure which should be considered for the front-line treatment of non-Hodgkin lymphoma patients with poor prognostic features.

Adult↗
PubMed1997

Long-term haematological reconstitution following BEAM and autologous transplantation of circulating progenitor cells in non-Hodgkin's lymphoma.

We report on long-term haematological recovery and clinical outcome after high-dose chemotherapy supported by circulating progenitor cells (CPC) transplantation in non-Hodgkin's lymphoma (NHL) patients, and analyse the role of variables which might influence engraftment. 63 consecutive NHL patients were enrolled in this study. Two groups of patients were considered for analysis: the first 34 patients had untreated diffuse large cell lymphoma with unfavourable prognostic factors. A second group of 29 patients underwent transplantation for resistant or relapsing NHL with low, intermediate and high grade histology. All patients received the BEAM conditioning regimen. As already reported in many studies, all patients showed a rapid haematological reconstitution. 43 patients (68%) achieved long-term complete trilineage engraftment within a median of 107 d from CPC transplantation. The neutrophil count was the first parameter reaching complete normalization, and haemoglobin was the last. Failure to meet the trilineage levels was due to lack of platelet recovery and was more frequent in patients transplanted in the setting of salvage protocols. By Kaplan-Meier analysis, the probability of a full reconstitution was 80% in patients to whom transplant was offered as part of a front-line therapy and 50% when transplant was given in the salvage programmes. Multivariate analysis showed that sustained long-term haematological reconstitution was significantly related to younger age, the time taken to achieve short-term reconstitution, and bone marrow involvement.

Adolescent↗
PubMed1997

Leiomyosarcoma of the inferior vena cava: novel surgical reconstruction preserves renal function.

Leiomyosarcoma of the inferior vena cava is rare and to date 145 cases have been reported. Here a new case of primary leiomyosarcoma of the inter-renal vena cava is reported. Surgical treatment consisted of excision of the vena cava on top of the renal arteries allowing radical resection. Reconstruction was original. The distal vena cava was sectioned and ligated just above the bifurcation and the free segment used to replace the excised part. In this the right venal vein was directly implanted. The left renal vein was reimplanted in the translocated segment via a venous (femoral vein) graft. Ligation of the distal vena cava was haemodynamically well-tolerated and the patient was free of symptoms at one year after operation. Control angiogram showed patency of the venous reconstruction. Early diagnosis is essential to improve patient survival, since it allows better radical resection, which is the only way of preventing the development of metastases.

Hemodynamics↗
PubMed1997

Hemodynamics following real and hypnosis-simulated phlebotomy.

Forearm arterial flow was measured in 22 healthy first-time blood donors during a 300-ml. blood letting and during the subsequent recovery. Blood pressure (BP) was also taken simultaneously and forearm peripheral resistance calculated. Following a transient BP and flow increase due to tachycardia related to needle insertion, both systolic BP and flow progressively and significantly decreased, while resistance increased. In a further 22 sex- and aged-matched highly hypnotizable subjects, blood donation was simulated by means of verbal hypnotic suggestions. The BP, flow and resistance curves were similar to those obtained with the real blood letting, without any between-subject difference or group/time interaction. Mere hypnosis without suggestion of phlebotomy and the simple bed resting did not produce any effect. These results indicate that the hemodynamic changes observed during and after a blood loss are partly due to mental involvement rather than merely to the hydraulic effects of the removal of blood.

Adult↗
PubMed1997

Distribution of capsular types and penicillin-resistance of strains of Streptococcus pneumoniae causing systemic infections in Argentinian children under 5 years of age. Streptococcus pneumoniae Working Group.

Streptococcus pneumoniae (SPN) is the most common cause of invasive infections in children, with high levels of mortality in developing countries. An increase in frequency of penicillin-resistant strains is reported in most parts of the world. A study was undertaken in Argentina and 5 other countries of the region, to determine the type distribution and penicillin resistance rate of SPN isolated from invasive infections in children less than 5 years old. Between June 1994 and March 1996, a total of 505 SPN isolated from sterile sites were collected from 15 hospitals located in 9 cities of different geographic areas. Clinical and epidemiological data from 443 children were analyzed. Sixty five percent SPN were isolated from children less than 2 years old. Pneumonia was the clinical diagnosis in 58% of the cases, meningitis in 22%, and sepsis in 10.6%. Isolates were recovered from blood (51.2%), pleural fluid (22.7%), CSF (20.7%), and other sterile sites (5.4%). Thirty different pneumococcal capsular types were identified and the 10 most frequent in descending order were: 14, 5, 1, 6A/6B, 7F, 9V, 19F, 19A, 16F y 23F, representing 89.3% of the total. Overall, 13.1% of isolates showed intermediate resistance to penicillin while 11.3% showed high resistance. Lethality was 8.8%, without correlation with penicillin-resistance and/or type. These result should be used in selecting the optimal combination of specific types for a conjugate vaccine, useful in children less than 2 years old and for considering therapeutic strategies for invasive pneumococcal infections.

Argentina↗
PubMed1997

Involvement of spinal recurrent inhibition in spasticity. Further insight into the regulation of Renshaw cell activity.

Changes in the excitability of the soleus H-reflex are were studied after oral administration of L-acetylcarnitine, a cholinomimetic substance, in eight healthy control subjects and 23 spastic patients presenting with slowly progressive paraparesis (n = 10), a cord lesion (n = 9) and a cerebral lesion (n = 4). Changes in the amount of recurrent inhibition of soleus motor neurons at rest were also estimated in order to assess the level of activity of Renshaw cells before and after L-acetylcarnitine administration. Recurrent inhibition elicited by a conditioning reflex discharge (H1) was assessed by a subsequent test reflex (H'). Four patients lacked an H' reflex. In approximately 50% of the remaining patients, recurrent inhibition was normal, while in the other half there was evidence of reduced or absent inhibitory activity at rest. Pooling the data relative to the effect of L-acetylcarnitine on the H-reflex in relation to the strength of recurrent inhibition disclosed that the ratio of peak-to-peak amplitude values of the maximum H reflex to maximum M wave responses (Hmax:Mmax) was reduced in all the cases in which the recurrent inhibition at rest was normal, while such a reduction was never observed in the patients in whom recurrent inhibition was found to be decreased at rest. In the former cases, the size of the H' reflex evoked by the same conditioning H1 discharge was further depressed after L-acetylcarnitine, pointing to a potentiating effect of the drug on Renshaw cells; in the latter cases no such effect was seen. A significant decrease in the mean Hmax:Mmax ratio after L-acetylcarnitine intake was also seen in the healthy control subjects. Possible changes in the amount of presynaptic inhibition on Ia terminals on soleus motor neurons after L-acetylcarnitine were ruled out. It is proposed that the differential effect of the drug on the H-reflex excitability is directly related to the level of Renshaw cell activity, a reduction of which probably follows a lesion interrupting reticulo-spinal pathways with tonic facilitatory influences on Renshaw cells. These findings support the hypothesis that Renshaw cell excitability is set via cortico-reticulo-spinal systems.

Acetylcarnitine↗