Sonia Tzantzoglou

Acetyl-carnitine deficiency in Aids patients with neurotoxicity on treatment with antiretroviral nucleoside analogues

Objective:A severe dose-limiting axonal peripheral neuropathy may develop in subjects on treatment with the nucleoside analogues didanosine (ddI), zalcitabine (ddC), and stavudine (d4T). The impairment of mitrochondrial DNA synthesis is crucial to the pathogenesis of this disorder although other mechanisms have not been ruled out. The depletion of acetyl-carnitine, which regulates the metabolism and function of peripheral nerves, could contribute to the neurotoxicity of these compounds. Design:Non-randomized, cross-sectional study of selected patients. Methods:We measured the serum levels of acetyl- and total carnitine in 12 subjects with axonal peripheral neuropathy developed on treatment with different regimens of neurotoxic nucleoside analogues (ddI, ddC, d4T). Subjects who did not develop peripheral neuropathy while staying on treatment with ddI (n = 10) or zidovudine (n = 11) served as the control groups. HIV-negative subjects with axonal or demyelinating autoimmune neuropathies (n = 10) and healthy individuals (n = 13) were additional control groups. Results:Subjects experiencing axonal peripheral neuropathy on treatment with ddI, ddC and d4T had significantly reduced levels of acetyl-carnitine in comparison to the control groups. No difference was observed in the levels of total carnitine between study subjects and the control groups. Conclusions:Our results demonstrate that subjects who developed peripheral neuropathy while staying on treatment with ddI, ddC and d4T had acetyl-carnitine deficiency. The normal levels of total carnitine in the study group appear to indicate the specificity of the defect and rule out coexisting relevant nutritional problems. The critical role of acetyl-carnitine for the metabolism and function of the peripheral nerves supports the view that the acetyl-carnitine deficiency found in these subjects may contribute to the neurotoxicity of ddI, ddC and d4T, even though the interference with mitochondrial DNA synthesis is regarded as the main cause of their toxicity.

Effect of Bifidobacterium bifidum and Lactobacillus acidophilus on gut mucosa and peripheral blood B lymphocytes

In 15 elderly individuals lyophilized Bifidobacterium bifidum (BB) and Lactobacillus acidophilus (LA) (Infloran) were administered in capsules (two capsules 4 times per day) for 28 days, while in 10 elderly controls placebo were given the same posology and for an equal period of time. The effects of this treatment on the immune system both at the periphery or the intestinal level were investigated. Results show that BB and LA significantly reduced the colonic inflammatory infiltration, without altering T, B and Leu7 + cell percentage. At the same time, a significant increase of B cell frequency in the peripheral blood was noted, in comparison to controls. The overall results suggest that the regular administration of BB and LA leads to a modulation of the immunological and inflammatory response in elderly subjects.

High Dose L-Carnitine Improves Immunologic and Metabolic Parameters in Aids Patients

Several reports indicate that systemic carnitine deficiency could occur in acquired immunodeficiency disease syndrome (AIDS), and that primary and secondary carnitine deficiency leads to critical metabolic dysfunctions. L-carnitine supplementation to peripheral blood mononuclear cells (PBMCs) of AIDS patients resulted in significant enhancement of the phytohemagglutinin (PHA)-driven proliferative response. High dose L-carnitine administration (6 gr per day for two weeks) to AIDS patients treated with zidovudine also led to increased PBMCs proliferation and reduced blood levels of triglycerides. In addition, a reduction of beta 2-microglobulin serum levels as well as circulating tumor necrosis factor (TNF)-alpha, mostly in patients exhibiting highly elevated levels, were found at the end of the treatment period. Our data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels. The mechanism(s) accounting for the observed results are currently not clear. Further studies are needed to confirm the hypothesis that L-carnitine affects the expression of HIV-induced cytokine.

L-carnitine deficiency in AIDS patients.

ObjectiveTo evaluate carnitine (3-hydroxy-4-N-trimethyl-ammoniobutanoate) deficiency in AIDS patients by measuring serum total, free and short-chain carnitine concentrations. DesignWe conducted an open study. SettingAll patients were seen at the Infectious Diseases Clinic, Università ‘La Sapienza’, Rome, Italy. Patients, participantsTwenty-nine AIDS patients, aged 27–41 years, with a previous history of drug use; and 14 healthy age-and sex-matched controls were studied. InterventionsStudy subjects were administered 500–800 mg zidovudine daily for 2 to 28 months (8 × 6 months). Main outcome measuresCarnitine deficiency was suspected in study participants prior to data collection because of previously reported cardiac symptoms, muscle weakness, hypometabolism and/or cachexia. ResultsA marked decrease in total and free carnitine was observed in 21 (72%) subjects. Nine of these patients also had low levels of short-chain carnitine. ConclusionsAIDS patients may become carnitine-depleted and therefore at risk for alterations in fatty-acid oxidation and energy supply.

Enhancement of host resistance against Salmonella typhimurium infection by a diet supplemented with yogurt

The effect of a diet supplemented with yogurt containing live lactobacilli (LAB) - Lactobacillus bulgaricus and Streptococcus thermophilus - on the response of inbred mice to infection with Salmonella typhimurium was elaborated. The results of our experiments were consistent with the hypothesis that modifications of the microflora influence the adherence of S. typhimurium to intestinal mucosa, the natural antibacterial activity of the Peyers patches lymphocytes, the accumulation of the macrophages in the liver, the proliferative responses of the splenocytes. The relationship between modifications of the immune response following ingestion of yogurt with live LAB and increased defense mechanisms was confirmed by the bacterial counts in livers and spleens and by the reduced mortality to S. typhimurium infection.

Inosine pranobex in the treatment of HIV infection : a review

Inosine pranobex (InPx) could prove a valuable and innovative approach to the treatment of HIV-infected patients, since InPx administration has been shown in two multicenter trials to effectively delay the progression of HIV infection to overt AIDS. However, further studies are strongly required to optimize both the dosage of inosine pranobex and the administration schedules. Furthermore, clinical trials evaluating combination therapy of HIV infection with both InPx and zidovudine should ultimately provide an important advance in the management of HIV-infected patients. Our finding that concomitantly administered InPx to zidovudine-receiving patients increased the plasma levels of zidovudine as well as prolonged zidovudine mean half-life during InPx treatment suggests several potential advantages of the combination treatment with both InPx and zidovudine, such as a need for lower zidovudine dosage and a longer interval period between administering zidovudine to obtain sustained plasma levels as well as a potential to enhance residue immune function resulting from inosine pranobex treatment.

Regulation of normal human polyrnorphonuclear leucocytes by carnitine.

The effect of carnitine, a drug that plays an essential role in mitochondria metabolism, on some of the most important human polymorphonuclear leucocytes (PMN) activation steps including modulation of adhesion molecule density, reactive oxygen species production, and tumour necrosis factor-α (TNFα) production was investigated. The capability of carnitine in protecting PMN from deter ioration on storage was also studied. Data shows that carnitine exerts considerable effects on all PMN functions investigated. Although the ultimate effect was often donor dependent, TNFα production was exceptional in that carnitine was able to consistently reduce TNFα production in Staphylococcus aureus stimulated PMN in a clear dose-dependent fashion. It is concluded that carnitine may represent a useful active agent in situations characterized by PMN mobilization/activation.

Clinical and immunologic effects of combination therapy with intravenous immunoglobulins and AZT in HIV-infected patients

30 patients with HIV infection were enrolled to evaluate the clinical efficacy and toxicity of zidovudine (AZT), 0.5 g/day p.o. (Group A) vs. AZT 0.5 g/day p.o. plus intravenous immunoglobulins (IVIG), 0.4 g/kg of body weight for three consecutive days, followed by one treatment of 0.6 g/kg of body weight every fourth week (Group B), over a period of one year. The study was open and randomized. The treatment groups were compared using the following study variables: 1) type of infections, recurrences and severity; 2) change in CD4+ T and CD8+ T cell count; 3) change in platelet count; 4) change in TNF alpha serum levels; 5) the probability of not developing an opportunistic infection over a period of 12 months. Patients from Group B developed less pathological events in comparison to Group A. No significative differences were evident with regard to values of T cell subsets obtained before and after treatment in each group and between the two groups. On the contrary, in 12 out of 15 patients from Group B there was a significant increase in platelet count. In both groups there was a significant decrease of mean serum levels of TNF alpha when a comparison was made between time 12 vs. time 6. However, when data were expressed as single values, in three subjects from Group B TNF alpha was still detectable by time 12 vs. 9 individuals in Group A. The cumulative probabilities of developing an opportunistic infection over the 12 months of treatment in the Group A subjects were significantly higher than in the Group B subjects (p less than 0.01). Adverse effects--nausea and gastric pain--were reported for 3 individuals (20%) from Group A and 4 patients (26%) from Group B. In conclusion, patients treated with AZT are especially likely to benefit from IVIG prophylaxis.

L-carnitine: a partner between immune response and lipid metabolism ?

The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

Open Randomized Controlled Parallel Study of Ofloxacin versus Trimethoprim-Sulfamethoxazole Treatment of Lower Respiratory Tract and Urinary Infections

A total of 60 patients with lower respiratory tract or urinary tract infections were enrolled in an open, randomized, controlled, parallel study comparing 300 mg ofloxacin (OFX) b.i.d. with trimethoprim + sulfamethoxazole (TMP 800 mg + SMX 160 mg), 1 tablet, b.i.d. The signs and symptoms of low respiratory tract infection were cured in 12 patients (80%) of the OFX group and improved in 2 other patients (13%); at the end of therapy, the 2 germs that persisted were Streptococcus pneumoniae and Branhamella catarrhalis. Clinical cure was achieved in 13 patients (86%) in the TMP-SMX group, while 2 patients were considered as failures (14%); after therapy, the 3 organisms that persisted were 2 S. pneumoniae and 1 Pseudomonas aeruginosa. As far as urinary tract infections are concerned clinical cure and complete eradication of bacteria were achieved in 14 patients in the OFX group (93%); the germ that persisted was Escherichia coli (100,000 CFU), but the patient was asymptomatic. In patients of the TMP-SMX group the urinary infections were cured in 11 subjects (73%); the germs that persisted were 2 E. coli and 1 Proteus mirabilis. Adverse effects were reported for 3 patients (10%) in the OFX group and 4 patients (13%) in the TMP-SMX group. The measurement of serum and intracellular (polymorphonuclear cells and lymphocytes) levels of OFX and TMP-SMX and the assessment of the hosts immunocompetence ruled out the possibility of any immunotoxicological side effect.