Increased formation of 8-iso-prostaglandin F(2alpha) is associated with altered bone metabolism and lower bone mass in hypercholesterolaemic subjects.

OBJECTIVES: To investigate the relationship of 8-iso-prostaglandin (PG) F(2alpha) levels, a reliable marker of in vivo oxidative stress and lipid peroxidation, with bone mineral density (BMD), bone turnover markers, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) in hypercholesterolaemia. DESIGN: Cross-sectional study. SETTING: University hospital centre. METHODS: Serum 8-iso-PGF(2alpha) levels were measured in 173 hypercholesterolaemic subjects and in 152 age- and sex-matched normocholesterolaemic controls. Femoral neck and lumbar spine BMD, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), OPG and RANKL levels, as well as urinary levels of C-terminal telopeptides of type I collagen (CTX-I), were also assessed. RESULTS: Hypercholesterolaemic subjects showed higher (P < 0.0001) serum 8-iso-PGF(2alpha) levels than controls. They also had decreased (P < 0.0001) femoral neck and lumbar spine BMD, and lower (P < 0.0001) serum BAP and OC levels. No significant differences between hypercholesterolaemic and control subjects were found when comparing urinary CTX-I levels, or serum OPG and RANKL levels. In multivariate linear regression analysis, serum 8-iso-PGF(2alpha) was the only negative predictor for femoral neck BMD and serum BAP and OC levels in hypercholesterolaemic subjects. No significant correlation (all P > 0.25) was present between serum 8-iso-PGF(2alpha) levels and urinary CTX-I levels, or serum OPG and RANKL levels, in hypercholesterolaemic subjects. CONCLUSIONS: We found an association between increased serum 8-iso-PGF(2alpha) levels and lower bone mass and reduced serum BAP and OC concentrations in hypercholesterolaemic subjects. These results would suggest a possible role for oxidative stress in the development of lower bone mass in hypercholesterolaemia.

Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory markers in patients with type 2 diabetes and peripheral arterial disease.

AIMS: To determine whether the G(-174)C interleukin 6 (IL-6) polymorphism influences the development of peripheral arterial disease (PAD) in individuals with type 2 diabetes. This was investigated by comparing the distribution of G(-174)C genotypes between patients with type 2 diabetes and PAD (PAD+) and those with type 2 diabetes but without PAD (PAD-). Plasma concentrations of IL-6, fibrinogen, C reactive protein (CRP), and vascular endothelial growth factor (VEGF) were also compared in PAD+ and PAD- patients. METHODS: Blood samples were collected from 146 PAD+ and 144 PAD- patients. SfaNI was used to determine the G(-174)C genotype. Plasma concentrations of IL-6, fibrinogen, CRP, and VEGF were measured by an enzyme linked immunosorbent assay. RESULTS: The GG genotype was more common in PAD+ patients than in PAD- patients. PAD+ patients also had increased mean plasma concentrations of IL-6, fibrinogen, CRP, and VEGF compared with PAD- patients. Mean plasma concentrations of IL-6, fibrinogen, and CRP in both PAD+ and PAD- patients were higher in those with the GG genotype than in those with the GC or CC genotypes. In contrast, mean plasma concentrations of VEGF in PAD+ and PAD- patients were not significantly different between those with different G(-174)C genotypes. CONCLUSIONS: These results support a model in which the GG genotype promotes PAD development among individuals with type 2 diabetes by inducing increased release of IL-6. Higher concentrations of IL-6 among those with the GG genotype is associated with increased plasma concentrations of fibrinogen and CRP.

Analysis of hepatitis C virus infection among health-care workers: an observational study.

AIM: Hepatitis C virus (HCV) is one of the most common blood-borne pathogens transmitted from patients to health care workers (HCWs). The Centers for Disease Control and Prevention (CDC) have developed a set of universal precautions to help prevent transmission of blood-borne pathogens between patients and HCWs in health care settings. HCV infection status among HCWs and proportion of HCWs experiencing occupational blood exposure accidents were monitored to assess the risk of HCV infection among HCWs at a hospital in Catania, Italy. METHODS: The number of HCWs reporting occupational blood exposure accidents during 1999 and 2004 were compared to examine whether there was any change in the incidence of these accidents among 900 HCWs. HCV infection status of these HCWs was also analyzed in 1999 and 2004 to determine how many were infected with HCV during this time period. RESULTS: HCV infection was detected in 21 out of 900 subjects in 1999. The remaining 879 HCWs remained HCV-negative until they were last tested in 2004. There was a statistically significant decrease in the number of HCWs that experienced occupational blood exposure accidents from 306 in 1999 to 240 in 2004 (P = 0.001). CONCLUSIONS: The finding that all 871 HCV-negative HCWs remained HCV-negative from 1999 until 2004 supports the view that the set of universal precautions recommended by the CDC are helpful for preventing HCV transmission from patients to HCWs. HCWs must continue following these precautions to prevent transmission of HCV and other blood-borne pathogens between patients and HCWs in the future.

Frequency of bcl-2/IgH translocation in patients with non-Hodgkin's lymphoma and chronic hepatitis C virus infection.

AIM: It has been previously suggested that t(14;18) translocation of bcl-2 to the immuno-globulin heavy chain (IgH) locus may contribute to pathogenesis of lymphoproliferative disorders related to hepatitis C virus (HCV) infection, including type II mixed cryoglobulinemia (MC). METHODS: In this study, the presence or absence of t(14;18) translocation was determined in tumor biopsy specimens and peripheral blood mononuclear cells (PBMCs) for 48 NHL patients with chronic HCV infection. RESULTS: In tumor biopsy specimens from 32 HCV-positive NHL patients, bcl-2/IgH translocation was detected in 1 of 13 patients with MC syndrome (7.7%) and 3 of 19 patients without MC syndrome (15.8%). In PBMCs from 23 HCV-positive NHL patients, this translocation was observed in 3 of 6 patients with MC syndrome (50%) and 4 of 17 patients without MC syndrome (23.5%). Interestingly, bcl-2/IgH translocation was found in 2 extranodal marginal zone B-cell lymphoma tissues from HCV-infected patients. CONCLUSIONS: However, additional studies are required to better clarify the relationship between this translocation and extranodal marginal zone B-cell lymphoma development. Although the frequency of bcl-2/IgH translocation in PBMCs from patients with chronic HCV infection is higher than that of other NHL patients, this increased translocation rate remains to be elucidated.

Persistent high plasma levels of interleukins 18 and 4 in children with recurrent infections of the upper respiratory tract.

The aim of this study was to examine whether children with recurrent infections of the upper respiratory tract might have alterations in the systemic immune response to viral infections as compared with healthy control children. We quantitated plasma levels of interferon-gamma, interleukin-12, interleukin-18, interleukin-4, lymphocyte subpopulations, serum immunoglobulins, and subclasses of immunoglobulin G in 30 children under the age of 6 years with recurrent infections of the upper respiratory tract, both during the acute phase of the infection and 4 weeks later, when clinical symptoms had resolved, as well as in 20 normal controls. We found elevated levels of immunoglobulin G primarily due to increased levels of immunoglobulin G(1). Moreover, significantly higher levels of interleukin-18 and interleukin-4 were noted during the acute phase of infection among children with an increased incidence of respiratory infections as compared with the controls (P =.022 and P =.0001, respectively), while plasma levels of interferon-gamma and interleukin-12 were significantly lower (P =.034 and P =.0001, respectively) than in controls. We suggest that an imbalance between T-cell helper type-1 and T-cell helper type-2 immune responses might be responsible for the perpetuation of recurrent infections of the upper respiratory tract.

Effects of ischaemic stress on leukocyte activation processes in patients with chronic peripheral occlusive arterial disease: role of L-propionyl carnitine administration.

An open study was carried out to assess whether, in patients with occlusive peripheral arterial disease (PAD), ischaemic stress induced by maximal physical exercise is associated with leukocyte activation processes, and to evaluate the effects of L-propionyl carnitine (LPC) administration on such processes. Fifteen patients with occlusive PAD (stage II-A), with a mean pain-free walking distance (PWD) of 199 +/- 70.66 m were orally treated with 2000 mg/day LPC for 2 months. Serum levels of E-selectin, P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-I (VCAM-1) were measured at rest and after the performance of a treadmill walking test (treadmill speed 3.5 km h(-1), inclination 12%) in the untreated condition, and again after treatment with LPC. Significant increases of these factors were observed after maximal exercise compared with resting values. Such increase was significantly reduced after LPC treatment compared with the untreated condition. This study shows that ischaemia induced by maximal stress is associated with leukocyte activation processes, and that LPC is capable of modulating these processes. LPC, therefore, may have a protecting role during ischaemia.

Cephalosporin-induced Hemolytic Anemia in a Sicilian Child.

A 27-month-old child developed acute hemolysis on two occasions after the administration of cephalosporin. On the first occasion, hemolysis was intravascular and was due to the formation of complexes between antibodies and the drug, which bound to red blood cells and caused severe hemolysis. On the second occasion, hemolysis was extravascular and was probably due to antibody-dependent cell mediated cytotoxicity. Marked increases in levels of CD19(+), and CD57(+) CD8(+) cells were detected among the subpopulations of the patient's lymphocytes but only in the level of CD19(+) cells from the patient's father, after incubation of a sample of whole blood with a solution of cephalosporins. These results might explain the differences between the immune response of the patient and those of other members of his family and of an unrelated control.

Cephalosporin-induced Hemolytic Anemia in a Sicilian Child; Erythropoiesis.

A 27-month-old child developed acute hemolysis on two occasions after the administration of cephalosporin. On the first occasion, hemolysis was intravascular and was due to the formation of complexes between antibodies and the drug, which bound to red blood cells and caused severe hemolysis. On the second occasion, hemolysis was extravascular and was probably due to antibody-dependent cell-mediated cytotoxicity. Marked increases in levels of CD(19) (+) and CD(57) (+) CD(8) (+) cells were detected among the subpopulations of the patient's lymphocytes but only in the level of CD(19) (+) cells from the patient's father, after incubation of a sample of whole blood with a solution of cephalosporins. These results might explain the differences between the immune response of the patient and those of other members of his family and of an unrelated control.

[Endothelin-1 variation in the coronary circulation during angioplasty with a stent implant]. / Variazione di endotelina-1 nel circolo coronarico durante angioplastica con impianto di stent.

Endothelin-1 (ET-1) is an endothelium-derived mediator with vasoconstrictive and mitogenic activity which stimulates vascular smooth muscle cell proliferation. The aim of this study was to evaluate ET-1 production during percutaneous transluminal coronary angioplasty (PTCA) and elective stent implantation. We hypothesized that the additional vessel wall trauma induced by stent deployment might be associated with a greater production of ET-1. To this end, ET-1 levels were measured in 18 patients undergoing PTCA and stenting (12 with left anterior descending coronary artery stenosis and 6 with circumflex artery lesion). The sampling sites were the coronary ostium and coronary sinus in basal conditions (before the procedure), during first balloon inflation, and 5, 20, 60 min after the end of first balloon inflation. At baseline, ET-1 levels were higher in the coronary sinus than in coronary ostium (1.58 +/- 0.22 vs 1.29 +/- 0.20 pg/ml, p < 0.001). During first balloon inflation, ET-1 coronary sinus levels significantly diminished with respect to the basal levels (1.08 +/- 0.32 vs 1.58 +/- 0.22 pg/ml, p < 0.001). Further significant variations of ET-1 levels were not detected neither following the first balloon inflation nor after stent deployment. In conclusion, the culprit lesion seems to produce most of ET-1 circulating in the coronary tree. This is demonstrated by higher ET-1 levels in the coronary sinus compared to coronary ostium at baseline, and even more by the significant ET-1 reduction in the coronary sinus during first balloon inflation. Despite our expectations, we did not detect any significant ET-1 increase during stent deployment.

Effect of alpha-interferon on natural killer cell activity and lymphocyte subsets in thalassemia patients with chronic hepatitis C.

The variation of natural killer (NK) cell activity and lymphocyte subsets 20 h after a single test dose of alpha-IFN, was studied in 17 thalassemic patients with chronic hepatitis C. All patients had suspended the alpha-IFN therapy at least 12 months before the study: 10 were considered responders and 7 nonresponders. Also NK cell cytotoxicity after in vitro incubation with alpha-IFN was studied. The administration of a single dose of alpha-IFN increased NK cell cytotoxic activity significantly in the group of responders and in non-responders; moreover the NK cell cytotoxic activity after alpha-IFN in vitro incubation increased both in responders and nonresponders, but to a lesser degree than in healthy controls. Absolute values of CD4+ and CD8+ lymphocytes decreased significantly only in responders. In conclusion, our data suggest that the variation of NK cytotoxic activity and lymphocyte subsets after a test dose of alpha-IFN can be considered a parameter related to IFN biological effects.

Efficacy of an analysis of lymphocyte subsets in predicting the clinical response to alpha-interferon therapy in thalassaemia patients with chronic infection by hepatitis C virus: a pilot study.

alpha-interferon (alpha-IFN) has been used to treat chronic non-A non-B hepatitis in thalassaemic patients with response rates from 45% to 83%. Unfortunately, treatment with alpha-IFN is associated with side-effects which have a negative effect on the quality of life of the patient. Therefore it would be useful if we could distinguish in advance those patients who would benefit from such therapy from those who would not. In the present study we found that the modification of lymphocyte subsets 20 h after the administration of the first dose of alpha-IFN revealed that relative numbers of T helper lymphocytes (CD4+) increased in three non-responding patients and decreased in five responding patients, whereas those of T suppressor lymphocytes (CD8+), and natural killer cells (CD57+, CD16+) decreased in non-responding patients and increased in responding patients. Therefore analysis of the lymphocyte subsets CD4, CD8, CD57 and CD16 before and 20 h after the administration of alpha-IFN can be used to predict the clinical response to treatment with alpha-IFN.

Plasma beta-endorphin levels and natural-killer cells in two cases of congenital indifference to pain.

We have investigated plasma beta-endorphin (beta-E), ACTH, and cortisol in two cases of congenital indifference to pain (CIP), a rare syndrome characterized by unresponsiveness to painful stimuli. As the two patients had frequent skin infections, we also studied lymphocyte response to mitogens in the absence or presence of beta-E. In addition, we explored a series of lymphocyte membrane antigens related to different aspects of the immune response, such as CD3+, CD4+, CD8+, B, NK Leu 7, Leu 9, and Leu 19, anti-interleukin-2 receptor (anti-TAC). Plasma beta-E levels in the two patients were significantly higher than in controls, whereas plasma ACTH and cortisol levels were normal. Lymphocyte response to the mitogen phytohemagglutinin was normal. The expression of Leu 7, Leu 9, and Leu 19, three antigens related to natural killer cells, was decreased by about 50%. The results indicate that in the two cases of CIP studied, high plasma beta-E levels are associated with a reduction in the expression of natural killer cells. This suggests that the two phenomena are specifically related to each other. These data represent further evidence of the possible pathophysiological relevance of the neuroendocrine-immune feedback.

Circulating immunocomplexes and laryngeal carcinoma.

Serum levels of circulating immunocomplexes (CIC) were studied in a group of 37 patients with laryngeal carcinoma using two polyethylene glycol-precipitation methods. The preoperative values of this group showed higher levels of CIC when compared with 140 normal controls. No correlation was noted between tumoral stage, oncotype, and serum levels of CIC. Previous studies have shown that the status of several different types of human tumors can be monitored by serial determinations of levels of CIC. We believe that this technique can be used to evaluate the efficacy of therapy and to detect the recurrence of laryngeal carcinoma.

[Determination of lactic dehydrogenase isoenzymes in precancerous and cancerous gastric mucosa]. / Determinazio degli isoenzimi della latticodeidrogenasi nella mucosa gastrica in corso di lesioni cancerose e precancerose.

We have studied modifications of LDH isoenzymes pattern in normal human gastric mucosa as well as in adenocarcinoma and precancerous lesions of the stomac (gastritis and ulcer); samples from the injured and the surrounding non-injured area were examined, drawing up the isoenzymes, using Tris-buffer pH 7,4 at 4 degrees C and performing the determination within 1 h - because of the high chronolability of the fractions LDH and LDH by cellogol electrophoresis separation. We have always noticed - especially in samples from adenocarcinoma- a shifting toward the M chains, with a clear increase of the fractions LDH4 and LDH5; this has been noticed even in the surrounding non-injured area.

Effects of ketoprofen on the calciuric and uricosuric activities of calcitonin in man.

The action of ketoprofen on the calciuric and uricosuric effects of porcine calcitonin in man is reported. The drug is capable of inhibiting both effects. This action is considered like an effect on CT receptors in the kidney or a competitive action on prostaglandin synthesis.