PubMed Health⌕ Search

Biomedical subjects

Giuseppe Famularo

Publications and source records attributed to Giuseppe Famularo.

At least 37 records · Page 2Linked to original sources
PubMed2004

Apoptogenic effect of fentanyl on freshly isolated peripheral blood lymphocytes.

BACKGROUND: Opioids may trigger the apoptotic death of widely ranging cell types, and apoptosis contributes to the immune deficiency of critically ill patients and subjects experiencing surgical trauma. There is evidence that an altered mitochondrial membrane potential constitutes an early and irreversible step in the death-signaling pathway of apoptosis. This study investigated whether fentanyl, a opioid widely used in the management of these patients, may induce apoptosis of T cells by altering their mitochondrial membrane potential. METHODS: Peripheral blood lymphocytes were cultured in the presence of 30 ng fentanyl for 60 (time 1), 90 (time 2), and 120 (time 3) minutes, respectively. The cells then were processed for assessment of mitochondrial membrane potential by means of flow cytometry and confocal scanning microscopy. Furthermore, production of reactive oxygen species, expression of the Fas-Fas L pro-apoptotic pathway, and apoptosis frequency were measured by means of flow cytometry. Control cells were incubated for the same times in the complete culture medium without the drug. RESULTS: Flow cytometry analysis showed a significantly increased rate (p < 0.05) of lymphocytes with disrupted mitochondrial membrane potential after incubation with fentanyl for 90 and 120 minutes, as compared with both control cells and lymphocytes cultured in the presence of fentanyl for 60 minutes. In addition, as early as 60 minutes after exposure to fentanyl, cells displayed a disrupted mitochondrial membrane potential when this was assayed by means of confocal laser scanning. These findings were associated with increased production of reactive oxygen species. The frequency of apoptotic lymphocytes was markedly increased (p < 0.05) after 120 minutes of incubation, as compared with untreated cells and cells exposed to fentanyl for only 60 and 90 minutes. Expression of Fas-FasL was not substantially affected by exposure to fentanyl. CONCLUSIONS: Fentanyl may induce a time-dependent apoptosis of lymphocytes by altering their mitochondrial redox metabolism.

Adult↗
PubMed2004

Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation.

Carnitine and its congeners may regulate the immune networks, and their influence on functions of immune cells predominantly or exclusively relies on carnitine-dependent energy production from fatty acids. A reduced pool of carnitines has been demonstrated in either serum or tissues, or both, from patients with a wide spectrum of disorders characterized by unregulated or impaired immune responses ranging from sepsis syndrome to systemic sclerosis, infection with human immunodeficiency virus, and chronic fatigue syndrome. Furthermore, experimental studies have consistently reported that the deranged immune responses and the less efficient inflammation towards infectious organisms associated with aging may be enhanced or modulated by treatment with carnitines. There is also evidence that carnitine deprivation could adversely affect the course of the sepsis syndrome, at least in experimental models, and preliminary studies suggest that carnitine deficiency is ultimately implicated in the pathophysiology of endotoxin-mediated multiple organ failure. Several data indicate that carnitine deficiency is a contributing factor to the progression of infection with human immunodeficiency virus, and carnitine therapy in those patients could counteract the unregulated process of lymphocyte apoptosis and improve CD4 counts. Some case reports have suggested the use of carnitine for the treatment of the severe lactic acidosis that complicates in some patients the use of reverse transcriptase inhibitors.

Animals↗
PubMed2003

Kikuchi Fujimoto lymphadenitis: case report and literature review.

We describe a young woman with two severe episodes of Kikuchi Fujimoto disease occurring 16 years apart. Both episodes were proven by biopsy, and on the second occasion the patient remained dependent on high-dose prednisone for more than 6 months in order to control inflammation and achieve a reduction in cervical lymph node size. The second lymph node biopsy showed leukocytoclastic vasculitis in addition to the typical features of Kikuchi Fujimoto disease, but, even though the clinical interpretation of this finding was unclear, we documented no clinical or laboratory evidence of the development of other serious systemic disease over 20 years of follow-up. Kikuchi Fujimoto disease is considered a disorder with a self-limited course and a favorable outcome. However, on the basis of our experience with this patient and data from peer-reviewed literature, we suggest that this generally accepted postulate should be revised.

Adult↗
PubMed2003

Jaundice and the sepsis syndrome: a neglected link.

The relationship between the sepsis syndrome and the development of jaundice is intriguing, with jaundice having been described as the presenting sign of septicaemia in very few cases. We describe a patient who developed a deep jaundice with conjugated hyperbilirubinaemia caused by Staphylococcus aureus during the early course of septicaemia, when no other sign of the sepsis syndrome could be recognised. It is generally accepted that a mild jaundice may complicate the course of the sepsis syndrome, but it is most unusual to observe such a protracted phase of jaundice before the emergence of other specific clinical signs and laboratory abnormalities. Clinicians should be aware of this presentation of the sepsis syndrome in order to avoid a potentially harmful delay in diagnosis and treatment.

Journal Article↗
PubMed2003

Probiotic lactobacilli: a new perspective for the treatment of inflammatory bowel disease.

Inflammatory bowel disease, such as ulcerative colitis and Crohn's disease, results from an interaction between susceptibility genes, the host's bacterial environment, gut barrier defects, and immunological factors. New management approaches have been evolved from advances in our understanding of the pathobiology of this common gut disorder In particular, the therapeutic manipulation of the bacterial microenvironment in the gut seems to offer an innovative tool for the treatment of those patients. Since the gut is a highly sensitizing organ that contributes to the systemic immune response, potent treatments need to be developed to reduce gut inflammation in this disorder. Recent studies have demonstrated that probiotic lactobacilli, and also immunostimulatory DNA sequences from those same bacteria have an important anti-inflammatory potential in this context. Future research should better define among patients with inflammatory bowel disease the various clinical phenotypes with the greatest potential of response to probiotic treatment. Identification of the genes leading to the disease and a rather better understanding of the underlying immunoregulatory abnormalities will be crucial steps to define the different profiles of interaction between endogenous digestive bacterial flora and the immune system in each individual patient. Such advances will probably lead to targeting of effective treatments, including bacteriotherapy with probiotic lactobacilli, to subsets of patients with inflammatory bowel disease.

Animals↗
PubMed2003

[Primary plasma cell leukemia. A fulminant case].

Primary plasma cell leukemia is a rare variant of malignant monoclonal gammapathies with de novo presentation in the leukemic phase. Only few series enrolling more than 20 patients have been reported in the literature. The authors deal with a patient who had a fulminant presentation of primary plasma cell leukemia with fatal outcome. Diagnosis of primary plasma cell leukemia was established based on Kyle's criteria, which include an absolute plasma cell count greater than 2 x 10(9)/L or a relative plasma cell number comprising greater than 20% of peripheral blood cells. The patient died within three days of diagnosis because of Streptococcus pneumoniae septic shock and multiple organ failure. This case report is worth of note due to the rarity of primary plasma cell leukemia and also because fulminant presentation is not commonly recognized among patients with malignant gammapathies.

Aged↗
PubMed2002

Modulation of apoptosis and improved redox metabolism with the use of a new antioxidant formula.

Oxidative stress is involved in the pathogenesis of a wide spectrum of diseases, implicating that strategies directed at counterbalancing oxidative processes could have a role in clinical medicine. There is also an evidence that oxidative stress acts as a major determinant of apoptotic cell death. Many studies have reported favourable effects of antioxidant formulas on several parameters of the oxidant-antioxidant balance, but none of them has focused whether antioxidant formulas could modulate apoptosis. We investigated in 20 healthy individuals the effect of supplementation with a formula containing alpha-tocopherol, alpha-lipoic acid, coenzyme Q(10), carnitines, and selenomethionine, on plasma oxidant status and peroxide levels, erythrocyte antioxidant enzymes, lymphocyte apoptosis, and generation of ROS at the mitochondrial level. Control subjects received only carnitines or an incomplete formula with alpha-tocopherol, alpha-lipoic acid, coenzyme Q(10), and selenomethionine. Supplementation with the complete formula resulted in a significant increase in the plasma antioxidant status that was mirrored by a decrease in blood peroxide levels and a reduced generation of ROS at the mitochondrial level. This was associated with a significant decrease in the frequency of peripheral blood lymphocytes, with either CD4 or CD8 phenotype, undergoing apoptosis. Less consistent results were found when either incomplete formula was used. Our study suggests that supplementation with antioxidant formulas can modulate the process of apoptosis under in vivo conditions. The clinical potential of this strategy in the treatment of diseases with an elevated commitment to apoptosis should be explored.

Adult↗
PubMed2002

Catastrophic antiphospholipid syndrome in a patient with Behçet's disease.

We report on a patient who had a life-threatening relapse of Behçet's disease associated with a catastrophic antiphospholipid syndrome. The patient experienced over a short time a recurrent acute myocardial infarction, multiple venous thromboses, uveitis, and erythema nodosum. Search for thrombophilic factors was positive only for lupus anticoagulant (LAC) and criteria for the diagnosis of the antiphospholipid antibody syndrome were fulfilled. LAC was not found three months after the discharge. At that time the patient had no evidence of clinically active disease or thrombosis. We suggest that LAC was the main triggering factor for the repeated thromboses in this patient.

Acute Disease↗
PubMed2002

L-carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine.

Apoptosis is critical to the progression of human immunodeficiency virus-1 (HIV-1) infection. It appears reasonable that antiretroviral therapies may not achieve a full control of the infection in the absence of an impact on apoptosis. We assigned 20 asymptomatic HIV-infected subjects with advanced immunodeficiency to receive either zidovudine (AZT), and didanosine (DDI) or the same regimen plus L-carnitine, a known antiapoptotic drug, for 7 months. Immunologic and virologic parameters were measured at baseline and after 15, 60, 120, and 210 days of treatment. We assessed on each time point the following: (a) the frequency of peripheral blood apoptotic CD4 and CD8 lymphocytes, CD4 and CD8 cells with disrupted mitochondrial membrane potential, and CD4 and CD8 cells undergoing oxidant stress; (b) the expression of the molecular markers of apoptosis Fas and caspase-1; and (c) the expression of p35/cdk-5 regulatory subunit that is involved in regulating cell survival and apoptosis. Absolute CD4 and CD8 counts and plasma viremia were also measured. Apoptotic CD4 and CD8 cells, lymphocytes with disrupted mitochondrial membrane potential, and lymphocytes undergoing oxidant stress were greatly reduced in subjects treated with AZT and DDI plus L-carnitine compared with those who did not receive L-carnitine. Fas and caspase-1 were down-expressed and p35 over-expressed in lymphocytes from patients of the L-carnitine group. No difference was found in CD4 and CD8 counts and viremia between the groups. No toxicity of L-carnitine was recognized. The addition of L-carnitine is safe and allows apoptosis and oxidant stress to be greatly reduced in lymphocytes from subjects treated with AZT and DDI.

Anti-HIV Agents↗
PubMed2002

Heat shock proteins and their role in heart injury.

Heat shock protein (HSP) synthesis arises transiently as a tool to protect cellular homeostasis after exposure to heat and a wide spectrum of stressful and potentially deleterious stimuli. HSPs are "molecular chaperones" that recognize and form a complex with incorrectly folded or denatured proteins, which ultimately leads to correct folding, compartmentalization, or degradation. Accumulating evidence has implicated HSPs as mediators of myocardial protection, particularly in experimental models of ischemia and reperfusion injury. Impaired myocardial performance, which results from many factors, including hypoxia, is one of the main mechanisms responsible for heart failure in the critically ill patient. In this setting, different protective functions have been attributed to HSPs, which include repairing ion channels, restoring redox balance, interacting with nitric oxide-induced protection, inhibiting proinflammatory cytokines, and preventing apoptosis pathway activation. On this basis, novel therapeutic strategies by means of promising pharmacologic interventions and/or gene transfection techniques are being investigated for their potential to enhance HSP expression by myocardial cells, with the goal of improving the outcome of the critically ill patient.

Apoptosis↗
PubMed2002

Nephrotoxicity and purpura associated with levofloxacin.

OBJECTIVE: To report a patient with lung cancer and idiopathic myelofibrosis with myeloid metaplasia who developed purpura and acute renal failure while receiving levofloxacin, and review the existing literature on quinolone nephrotoxicity. CASE SUMMARY: A 73-year-old white man, with a medical history of non-small-cell lung cancer and idiopathic myelofibrosis with myeloid metaplasia, was prescribed levofloxacin because of a lower urinary tract infection. Three days later, he presented with palpable purpura and erythematous skin lesions over the lower limbs and trunk, with a markedly reduced urinary output. Serum creatinine and urea nitrogen were 6.4 and 190 mg/dL, respectively. Levofloxacin was discontinued, and prednisone, furosemide, and intravenous fluids were given. The patient fully recovered over the ensuing 4 weeks. CONCLUSIONS: Nephrotoxicity associated with levofloxacin is uncommon. Allergic interstitial nephritis or vasculitis is believed to be the underlying pathologic process. Definitive diagnosis requires performance of renal biopsy, although this is not always feasible. In this case, a return of renal function to normal, with the disappearance of purpura following the discontinuation of levofloxacin and corticosteroid treatment, supports the presumptive diagnosis of a hypersensitivity reaction to levofloxacin.

Acute Kidney Injury↗