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R Lodi

Publications and source records attributed to R Lodi.

At least 73 records · Page 4Linked to original sources
PubMed1996

Inorganic phosphate is transported into mitochondria in the absence of ATP biosynthesis: an in vivo 31P NMR study in the human skeletal muscle.

We used 31-phosphorus magnetic resonance spectroscopy to study in vivo the transport of inorganic phosphate (Pi) from cytosol into mitochondria as assessed by the kinetics of Pi recovery during ischemia after aerobic exercise in human skeletal muscle. In all subjects during the first 30 s of ischemia inorganic phosphate showed a marked decrease from the value measured at the end of exercise, whilst phosphocreatine maintained the same value reached at the end of exercise. Our results show that Pi transport from cytosol into mitochondria is active in the absence of ATP biosynthesis and lasts 30 s possibly as a consequence of a decreased pH gradient, due to symport of Pi and H+ associated with an inactive electron transport chain during ischemia.

Adolescent↗
PubMed1996

Partial block of glycolysis in late-onset phosphofructokinase deficiency myopathy.

A late-onset, myopathic variant of phosphofructokinase (PFK) deficiency has been previously described in two patients of Ashkenazic descent. We report here on a non-Ashkenazic woman with the onset, at the age of 48 years, of a progressive limb girdle myopathy that was not preceded by a history of exercise intolerance. Muscle biopsy findings at the age of 58 years showed deposition of amylopectin-like material in muscle fibers and the absence of histochemical PFK activity. Enzymatic PFK activity in vitro was only 4% of normal. Since the forearm ischemic exercise test induced a sub-normal production of serum lactate, the patient underwent phosphorus magnetic resonance spectroscopy (31P-MRS), a non-invasive method that allows in vivo assessment of the functional status of the glycolytic pathway and mitochondrial oxidative metabolism by measuring the high-energy phosphates and cytosolic pH. In vivo, 31P-MRS disclosed a residual glycolytic flux and a normal rate of ATP production both at rest and during exercise. These results suggest that, in some patients, muscle PFK deficiency may be partial in vivo, and more severe in vitro, possibly due to protein or mRNA instability rather than absence. The presence of these findings in a patient with the late-onset myopathic form is compatible with a distinct pathogenetic mechanism, relying on progressive polysaccharide accumulation, rather than on acute energetic shortage in muscle fibers.

Female↗
PubMed1996

Autosomal dominant limb girdle myopathy with ragged-red fibers and cardiomyopathy. A pedigree study by in vivo 31P-MR spectroscopy indicating a multisystem mitochondrial defect.

We describe a late-onset autosomal dominant limb girdle myopathy, associated with dilated cardiomyopathy and mental deterioration. In two affected members of the pedigree with histochemical (ragged-red and cytocrome c oxidase - negative fibers) and ultrastructural abnormalities of muscle mitochondria, in vivo muscle phosphorus MR spectroscopy disclosed a slow rate of phosphocreatine resynthesis after exercise. Brain phosphorus MR spectroscopy revealed a defect of the energy metabolism in the two patients and in a third asymptomatic member, as shown by a significantly low phosphocreatine, increased ADP and decreased phosphorylation potential. Molecular analysis of muscle mitochondrial DNA failed to reveal any known mutation, including multiple deletions of the mtDNA which have been associated with some autosomal dominant mitochondrial diseases. The multisystem clinical involvement, the presence of ragged-red fibers and the alterations revealed by in vivo brain and muscle 31P-MRS suggest that this limb-girdle syndrome represents an unusual phenotype of mitochondrial cytopathy.

Adult↗
PubMed1996

Improvement of pulmonary graft after storage for twenty-four hours by in vivo administration of lazaroid U74389G: functional and morphologic analysis.

BACKGROUND: We examined the effects of in vivo administration of a potent inhibitor of iron-dependent lipid peroxidation, lazaroid U74389G, on lung preservation. METHODS: Lungs isolated from Sprague-Dawley rats (n = 23) were either immediately reperfused after removal (control, n = 8) for 2 hours by means of an isolated, pulsatile blood perfusion system or reperfused after cold storage (4 degrees C) for 24 hours in the University of Wisconsin solution with (n = 7) or without (n = 8) lazaroid. The lazaroid group had in vivo infusion of lazaroid U74389G (6 mg/kg) before lung harvest plus addition to the perfusate (50 mu mol/L) at the onset of reperfusion. Routine aerodynamics, hemodynamics, and blood gases were assessed during the perfusion period. Lipid peroxidation in the lung tissue was assayed with the thiobarbituric acid-reactive product, malondialdehyde. Histologic evaluation was performed with light microscopic and transmission electron microscopic analyses. RESULTS: All lungs in the University of Wisconsin solution group (24-hour storage without lazaroid) failed within 1 hour of reperfusion. Lungs in control and University of Wisconsin solution + lazaroid group survived the 2-hour perfusion period. University of Wisconsin solution + lazaroid group showed significantly better arterial oxygen tension values relative to those in the University of Wisconsin solution group (control, 85.2 +/- 1.9; University of Wisconsin solution, 53.9 +/- 3.2 [p < 0.05 versus control group and University of Wisconsin solution + lazaroid]; University of Wisconsin solution + lazaroid, 74.8 +/- 1.4; arterial oxygen tension (mm Hg) at 30 minutes). Lipid peroxide in University of Wisconsin solution + lazaroid group was significantly lower than that of the University of Wisconsin solution group (65.0 +/- 5.0 versus 495 +/- 105 nmol malondialdehyde/gm wet lung tissue; p < 0.01). Transmission electron microscopic analysis showed that University of Wisconsin solution + lazaroid group significantly attenuated lung damage when compared with University of Wisconsin solution group. CONCLUSION: Administration of lazaroids in vivo before organ harvest and in situ at the onset of the reperfusion enhances lung preservation in this model.

Animals↗
PubMed1995

Enhancement of extended lung preservation with a vasoactive intestinal peptide-enriched University of Wisconsin solution.

Vasoactive intestinal peptide (VIP) is a known pulmonary and bronchial vasodilator as well as an oxygen free radical scavenger. Since its effect as an additive to University of Wisconsin (UW) solution for lung preservation has been shown previously, the aim of this study was to determine the ability of VIP to improve lung preservation followed by reperfusion. Four groups of excised Sprague-Dawley rat lungs (n = 24) were studied using an isolated blood perfused working lung model. The first 3 groups of lungs were flushed and stored in UW solution at 4 degrees C for: (1) 4 hr, (2) 18 hr, and (3) 24 hr. Group 4 lungs were flushed with UW solution + VIP (1 microgram/ml) and stored in UW solution + VIP (0.5 microgram/ml) for 24 hr. After preservation, the lungs were reperfused to evaluate their functions for 2 hr or until lung failure occurred (arterial oxygen saturation less than 90% and/or appearance of bronchial fluid in the bronchial cannula). In the lungs stored in UW solution for 24 hr, failure occurred after 10 min of reperfusion and all functions were significantly altered. The addition of VIP to UW solution maintained the functional capacity of the lungs, recorded by lung resistance, lung compliance, elastic work, flow resistive work, shunt fraction, and blood oxygen tension. No statistical difference in these parameters other than shunt fraction was found when the VIP group was compared with the group preserved for 4 hr in UW solution. We conclude that lung preservation can be extended to 24 hr with the maintenance of lung functional capacity if VIP is added to UW solution.

Adenosine↗
PubMed1995

Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy.

A woman affected by chronic progressive external ophthalmoplegia and muscle mitochondrial DNA deletion was studied by phosphorus magnetic resonance spectroscopy (31P-MRS) prior to and after 1 and 7 months of treatment with oral lipoic acid. Before treatment a decreased phosphocreatine (PCr) content was found in the occipital lobes, accompanied by normal inorganic phosphate (Pi) level and cytosolic pH. Based on these findings, we found a high cytosolic adenosine diphosphate concentration [ADP] and high relative rate of energy metabolism together with a low phosphorylation potential. Muscle MRS showed an abnormal work-energy cost transfer function and a low rate of PCr recovery during the post-exercise period. All of these findings indicated a deficit of mitochondrial function in both brain and muscle. Treatment with 600 mg lipoic acid daily for 1 month resulted in a 55% increase of brain [PCr], 72% increase of phosphorylation potential, and a decrease of calculated [ADP] and rate of energy metabolism. After 7 months of treatment MRS data and mitochondrial function had improved further. Treatment with lipoate also led to a 64% increase in the initial slope of the work-energy cost transfer function in the working calf muscle and worsened the rate of PCr resynthesis during recovery. The patient reported subjective improvement of general conditions and muscle performance after therapy. Our results indicate that treatment with lipoate caused a relevant increase in levels of energy available in brain and skeletal muscle during exercise.

Adenosine Diphosphate↗
PubMed1995

Myophosphorylase deficiency affects muscle mitochondrial respiration as shown by 31P-MR spectroscopy in a case with associated multifocal encephalopathy.

We report here a glycogen storage myopathy type V associated with multifocal encephalopathy. The patient, a 43-year-old male with increased serum CK, a heavy drinker and smoker, had been affected by generalized epilepsy since age 24, after a cranial injury. He had had a right hemiparesis 2 years before coming to our observation and a transient left hemiparesis the following year. CT and MRI of the brain showed multiple hemispheric lesions consistent with an ischemic process, as suggested by single photon emission tomography of the brain. Muscle biopsy showed a vacuolar myopathy, and myophosphorylase activity was 13% of the normal mean. Phosphorus magnetic resonance spectroscopy (31P-MRS) performed on resting calf muscles showed increased PCr to ATP and decreased PCr to P(i) ratios. During both aerobic and ischemic exercise 31P-MRS failed to show any cytosolic acidification and phosphomonoesters (PME) accumulation, two MRS findings in agreement with McArdle's syndrome diagnosis. Mitochondrial respiration was also affected as shown by a low PCr to P(i) ratio at rest and by a low rate of PCr re-synthesis during recovery from aerobic exercise. This latter finding in McArdle's disease can be explained by decreased mitochondrial substrate availability, which in turn can contribute to the phenotypic manifestations of the disease.

Adult↗
PubMed1995

Epilepsia partialis continua associated with NADH-coenzyme Q reductase deficiency.

We report the clinical, neuroradiological and biochemical features of a patient with epilepsia partialis continua (EPC). MRI studies disclosed multiple cortico-subcortical areas of abnormal signal intensity. The activity of complex I of the mitochondrial respiratory chain was markedly reduced in skeletal muscle. The biochemical defect was reflected in vivo by a failure of brain and skeletal muscle bioenergetics, as shown by exercise and phosphorus magnetic resonance spectroscopy (31P-MRS) studies. Muscle morphology was repeatedly normal, and molecular genetic analysis of mitochondrial DNA was not informative. On the basis of in vivo and in vitro findings, the observed defect of the mitochondrial respiratory chain was considered the underlying biochemical pathogenesis of the disease. The observation of an oxidative defect in the brain and skeletal muscle of a patient with EPC emphasizes the importance of studying mitochondrial energy metabolism in patients with EPC not associated with primary CNS lesions when clinical and morphological findings suggesting a mitochondrial disorder are lacking. 31P-MRS can be a useful method to uncover deficits of CNS mitochondrial function and provide the indication for further biochemical studies.

Adult↗
PubMed1995

Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine.

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder of unknown pathogenesis characterized by migraine and transitory hemiplegic attacks. We describe a kindred fulfilling the diagnostic criteria for FHM in which: (1) brain phosphorus magnetic resonance spectroscopy (31P-MRS) showed a reduced phosphocreatine content accompanied by high [ADP], high percentage of V/Vmax of ATP biosynthesis and decreased phosphorylation potential; (2) muscle 31P-MRS showed a reduced rate of phosphocreatine recovery after exercise; (3) blood lactate was increased after effort; (4) muscle biopsy showed, in one patient, rare ragged red fibers succinate-dehydrogenase positive and cytochrome c oxidase negative; (5) genetic analysis of muscle mitochondrial DNA did not show any of the two point mutations in the tRNA(Leu(UUR)) associated with the MELAS syndrome (Mitochondrial myopathy, Encephalopathy with Lactic Acidosis and Stroke-like episodes). The defective energy metabolism of brain and muscle found in this pedigree suggests a multisystemic disorder of mitochondrial function in this FHM pedigree.

Adolescent↗
PubMed1995

"Yellow nail syndrome" associated with chronic recurrent pericardial and pleural effusions.

The authors describe a case of yellow nail syndrome in a 44-year-old male patient, with a clinical picture characterized by hand and foot onychodystrophy, lymphedema in the legs and recurrent pleural and pericardial effusions. They indicate subxiphoid pericardiostomy and pleural drainage as the rational surgical procedure for the treatment of this particular associated pathology.

Adult↗
PubMed1995

Defective brain and muscle energy metabolism shown by in vivo 31P magnetic resonance spectroscopy in nonaffected carriers of 11778 mtDNA mutation.

In vivo phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective brain and muscle energy metabolism in three affected siblings in a family with Leber's hereditary optic neuropathy (LHON) with the 11778 mtDNA mutation. We studied 14 nonaffected members of the same pedigree by 31P-MRS and molecular genetics. Nine of 14 individuals studied had the 11778 mtDNA mutation, with various degrees of heteroplasmy. A decreased brain energy reserve, as shown by low phosphocreatine content and phosphorylation potential and high [ADP], was present in eight of these nine subjects with the 11778 mutation. A low rate of postexercise phosphocreatine recovery in muscle was present in six of the nine mutated individuals. Normal MRS findings in the brain of one and the muscle of three carriers were accompanied by a low percentage of mutated mtDNA. All subjects without mutation had normal brain and muscle MRS. 31P-MRS disclosed defective bioenergetics in the brain or muscle or both of all asymptomatic carriers studied from our pedigree.

Adenosine Diphosphate↗
PubMed1994

The use of phosphorus magnetic resonance spectroscopy to study in vivo the effect of coenzyme Q10 treatment in retinitis pigmentosa.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has emerged as a noninvasive reliable tool for in vivo study of human tissue bioenergetics. It detects and quantifies some phosphorylated compounds present in millimolar concentration inside the cell, including ATP, phosphocreatine (PCr) and inorganic phosphate (Pi). By 31P-MRS we studied brain and skeletal muscle energy metabolism of three patients with retinitis pigmentosa before and after oral coenzyme Q10 (CoQ10) (100 mg/day). Before treatment we found a low PCr content in the brains of all patients, accompanied by a high [Pi] and high [ADP]. In two of three patients CoQ10 treatment resulted in a larger brain energy reserve mainly shown by an increased [PCr]. Abnormal muscle mitochondrial function was found only in one patient as shown by a reduced rate of PCr resynthesis after exercise. In this patient CoQ10 treatment resulted in an increased rate of PCr resynthesis. Our observations indicate that CoQ10 can improve mitochondrial functionality in the brain and skeletal muscle of patients with retinitis pigmentosa.

Adenosine Triphosphate↗
PubMed1994

Brain and muscle energy metabolism studied in vivo by 31P-magnetic resonance spectroscopy in NARP syndrome.

Phosphorus magnetic resonance spectroscopy (31P-MRS) was used to study in vivo the energy metabolism of brain and skeletal muscle in two members of an Italian pedigree with NARP syndrome due to a point mutation at bp 8993 of mtDNA. In the youngest patient, a 13 year old girl with retinitis pigmentosa, ataxia, and psychomotor retardation, there was an alteration of brain energy metabolism shown by a decreased phosphocreatine content, increased [ADP] and decreased phosphorylation potential. The energy metabolism of her skeletal muscle was also abnormal, as shown by resting higher inorganic phosphate and lower phosphocreatine concentrations than in normal subjects. Her mother, a 41 year old woman with minimal clinical involvement, showed a milder derangement of brain energy metabolism and normal skeletal muscle. Findings with MRS showed that this point mutation of mtDNA is responsible for a derangement of energy metabolism in skeletal muscle and even more so in the brain.

Adenosine Diphosphate↗
PubMed1994

31P-magnetic resonance spectroscopy in migraine without aura.

We investigated 22 patients with migraine without aura, all drug-free and in headache-free periods, by means of 31P-magnetic resonance spectroscopy (MRS) of brain and muscle. Brain 31P-MRS showed significantly low phosphocreatine, increased adenosine diphosphate, and decreased phosphorylation potential. There was a slow rate of phosphocreatine recovery after exercise in the muscle of 12 of 22 patients. Energy metabolism is abnormal in migraine without aura, as previously demonstrated in patients with migraine stroke and migraine with aura.

Adolescent↗
PubMed1993

Further impairment of muscle phosphate kinetics by lengthening exercise in DMD/BMD carriers. An in vivo 31P-NMR spectroscopy study.

We used phosphorus magnetic resonance spectroscopy (31P-MRS) to study the effect of exercise-induced muscle injury in the calf muscle of 7 DMD/BMD carriers and 6 non-carrier females. All subjects performed 50-80 lengthening contractions with the right calf muscles. 48 h after lengthening exercise non-carriers showed increased sensitivity to pressure in their gastrocnemius accompanied by increased T2 relaxation times and by elevated Pi/PCr ratios at rest. DMD/BMD carriers did not show any effect of lengthening exercise on these measurements. In-magnet exercise revealed in all carriers a reduced initial rate of Pi recovery and an increased time to fully recovery the resting value of intracellular pH. Lengthening exercise further decreased the initial rate of Pi recovery. Non-carriers did not show any variation attributable to lengthening exercise either during in-magnet work or during recovery from exercise. We found that lengthening exercise contractions causes: (1) less muscle injury in carriers compared to non-carriers, (2) even slower rate of Pi recovery, but (3) no effect on Pi recovery in non-carriers. The use of lengthening exercise and measurements of Pi recovery may be a useful method to evaluate the disease process in DMD/BMD.

Adolescent↗
PubMed1993

Defective brain energy metabolism shown by in vivo 31P MR spectroscopy in 28 patients with mitochondrial cytopathies.

We studied brain energy metabolism by phosphorus magnetic resonance spectroscopy (31P MRS) in 28 patients with mitochondrial cytopathies, and 20 normal control subjects. Fourteen patients had myopathy alone, six had only mild brain symptoms, and eight showed different degrees of brain involvement. Brain 31P MRS showed a low phosphocreatine content in all patients, accompanied by a high inorganic phosphate in 14 of 28 patients. The average value of the Pi concentration in the patient group was significantly (p = 0.009) different from the control group. The cytosolic pH was normal. From these data were derived a high concentration of ADP (calculated from the creatine kinase equilibrium), a high percent value of V/Vmax for ATP biosynthesis, and a low phosphorylation potential, all features showing a derangement of brain energy metabolism, in all patients with mitochondrial cytopathies. 31P MRS proved to be sensitive enough to disclose a deficit of mitochondrial functionality not only in the affected patients, but also in those without clinically evident brain symptoms.

Adenosine Diphosphate↗
PubMed1993

Influence of different harvesting techniques on the arterial wall of the internal mammary artery graft: microscopic analysis.

An histological comparison was made between left internal mammary arteries (LIMAs) harvested and prepared with different techniques prior to coronary artery bypass grafting. The mobilization of LIMA was made as follows: conventional technique (group I), extra pleural takedown with lysis of the endothoracic fascia (group II), and LIMA skeletonization (group III). Each group was divided into two other sub-groups according to the LIMA graft preparation: papaverine-saline solution sprayed on the pedicle (sub-group A) and intraluminal hydrostatic dilatation (sub-group B). Free blood flow from the LIMAs was measured immediately before cardiopulmonary bypass and ultrasonic duplex scanning (UDS) was performed to analyze the flow patterns and velocities during the early postoperative course. The results showed that the technique by which the LIMA is harvested bears no significant relationship to microscopical graft damage, while intimal lesions were observed in all sub-groups that adopted intraluminal hydrostatic dilatation (sub-group B). No difference in intraoperative LIMA flows were noted between groups and sub-groups of patients except in the case of group I-sub-group B, in which the flow was markedly reduced. Intramural haematoma or subadventitial blood effusion was observed with low incidence and magnitude in all groups and subgroups of patients, without any reduction of blood flow, and all LIMAs were patent at UDS measurements. In conclusion, the results showed that the method by which the IMA is harvested bears little and insignificant relationship to arterial wall damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗