Diltiazem modulates monokine production in human mixed lymphocyte culture.

BACKGROUND: Calcium channel blockers are widely used in transplantation. Their immunosuppressive activity is well known and has been demonstrated both in vitro and in vivo. Nevertheless, their effect on cytokine production has never been reported. METHODS: One-way mixed lymphocyte cultures (MLCs) have been obtained from healthy human subjects. Cytokine production has been assessed by three different methods: by enzyme-linked immunosorbent assay on supernatants of MLC, by enzyme-linked immunospot method on MLC cells for measuring cytokine-producing cells, and by the reverse transcription polymerase chain reaction technique on MLC cells for measuring cytokine mRNAs. RESULTS: An interesting effect on proinflammatory monokines was observed: in this study, we demonstrate that the calcium antagonist diltiazem enhances interleukin-1beta and slightly reduces interleukin-6 production in MLC, but it has no effect on tumor necrosis factor-alpha levels. CONCLUSION: For the first time, a modulation of monokine production by diltiazem can be demonstrated. This evidence suggests that calcium antagonist drugs may exert effects on monocytes and possibly on other antigen-presenting cells.

Further evaluation of autoreactive T cells in hydatid patients.

We evaluated the peripheral autoreactive response in patients with Echinococcus granulosus who showed a negative humoral response as compared to seropositive patients and healthy controls. For this purpose, a limiting dilution analysis (LDA) of autologous mixed lymphocyte cultures was established to both estimate frequency of autoreactive T cells and, by analysing the shape of the curves, to clarify the mechanisms that underlie the autoreactive response. Different LDA curves were observed between healthy controls and patients, suggesting that different cell interactions are involved in the two populations. More interestingly, all hydatid patients, independent of their humoral response, showed a higher number of autoreactive T cells than controls. Precisely, subjects with a negative humoral response showed a range of values for autoreactive T cells exactly between the value ranges observed in seropositive and normal subjects. The present data also show that the increase of autoreactive T cells in hydatid patients correlates with the production of specific antibodies.

Autoreactive response in seronegative homosexual men at high risk for HIV infection.

Peripheral autoreactive T cell response was evaluated by limiting dilution analysis of autologous mixed lymphocyte reaction cultures in 15 subjects at high risk for HIV infection and in 20 normal individuals. The two groups did not show a quantitative difference of peripheral autoreactive T cells, but they showed different kinetics. While controls provided a straight line passing through the origin, the majority of high risk individuals showed a curve with a limited linear portion at high cell concentration, indicating that different mechanisms regulate the autoreactive response in the two groups studied. A follow-up study performed in three high risk and three normal individuals revealed a time-dependent increase of peripheral autoreactive T cells only in high risk subjects. Such increase correlates with the decrease of CD4+ cell number and CD4+/CD8+ cell ratio. Furthermore, the proliferative response of the same three subjects to gp160 peptides suggests a specific cellular reactivity to HIV components. This work has potential importance in understanding some of the early events in HIV infection.

Food allergy and infantile autism.

The etiopathogenesis of infantile autism is still unknown. Recently some authors have suggested that food peptides might be able to determine toxic effects at the level of the central nervous system by interacting with neurotransmitters. In fact a worsening of neurological symptoms has been reported in autistic patients after the consumption of milk and wheat. The aim of the present study has been to verify the efficacy of a cow's milk free diet (or other foods which gave a positive result after a skin test) in 36 autistic patients. We also looked for immunological signs of food allergy in autistic patients on a free choice diet. We noticed a marked improvement in the behavioural symptoms of patients after a period of 8 weeks on an elimination diet and we found high levels of IgA antigen specific antibodies for casein, lactalbumin and beta-lactoglobulin and IgG and IgM for casein. The levels of these antibodies were significantly higher than those of a control group which consisted of 20 healthy children. Our results lead us to hypothesise a relationship between food allergy and infantile autism as has already been suggested for other disturbances of the central nervous system.

Immunoregulatory effect of a synthetic peptide corresponding to a region of protein p24 of HIV.

The effect of a synthetic peptide, corresponding to a sequence of HIV-1 p24 protein (amino acids 218-237), on in vitro immune responses was studied. The peptide inhibited in a dose-dependent manner the induction of an anti-SRC antibody response and of a PPD-specific proliferative response of human PBL. On the other hand, PHA-induced proliferation of human PBL and PPD-induced proliferation of a PPD-specific human T-cell line were not modified by comparable amounts of the peptide. These results suggest that structures from a protein (p24), present in the serum throughout the course of HIV infection, are able to interfere with the inductive stages of specific immune responses. These findings may help to unravel some of the pathogenic mechanisms of AIDS and may contribute to the development of vaccine strategies.

A 5-year analysis of organ donors and recipients in Italy.

This article describes the improvement of organ donation and transplantation in Italy during 1995-1999. In 1999, the mean number of donors per million population reached 13.7 in Italy. In addition, an analysis regarding major characteristics of donors and recipients is presented, focusing particularly on donor characteristics that have changed in the past 5 years. Despite the encouraging results, further efforts are required to reach the European mean, which still remains higher than the Italian national mean. In particular, an increase of organ donation and procurement in regions with a poor activity in this field is crucial. A 1999 law on donation and transplantation should help in solving problems that continue to affect part of the nation, especially preparing the healthcare staff dedicated to organ retrieval to promote organ procurement.

[Organ donation, retrieval, and transplantation in Italy, in 1994-98]. / Donazioni, prelievi e trapianti di organo in Italia, anni 1994-98.

Organ donation and transplantation activity in Italy have been always characterised by two contrasting features: first the constant positive trend in the improvement of the number of organ donors and transplants which allowed the country to exceed the value of 12 donors per million population in 1998; second the difficult situation in southern regions, so that the national distribution of the activity is highly and steadily non homogeneous. Herein we report the data regarding donation, retrievals and transplant activity in Italy in the years 1994-98, focusing on the activity of each region and the three interregional centres which encompass the majority of the national territory.

[National quality control of serologic HLA typing]. / Controllo nazionale di qualità della tipizzazione sierologica HLA.

Since 1995 the Istituto Superiore di Sanità, in collaboration with the Italian Red Cross, has been organising annually the quality control of serological HLA class I and II typing on histocompatibility laboratories which perform typing for organ and bone marrow transplantation. Improvement has been obtained every year; in fact, results of the 1997 control show that the 77% of the laboratories typed the major specificities correctly. Despite the remarkable improvement achieved during the first three years of quality controls, a new organisation has been designed for further years to ensure the participation of all the Italian laboratories (more than 100) and to promote a quality control scheme that will be acceptable at international level.

Triploid partial molar pregnancy and fetal neural tube defect detected through Down's syndrome screening.

A third case of triploid partial molar pregnancy with fetal neural tube and abdominal-wall defect, detected through maternal serum alphafetoprotein and hCG screening for Down's syndrome is reported. A 23-year-old woman had elevated serum alphafetoprotein and hCG levels at routine screening at the 16th week of gestation. Ultrasound examination suggested a fetal neural tube and abdominal-wall defect with thickened placenta. Amniocentesis was performed. A triploid karyotype (69 XXY) was confirmed with standard cytogenetic analysis. Fetal neural tube and abdominal wall defect was confirmed at the autopsy of the fetus. Placental histology was consistent with a hydatiform mole. When serum alphafetoprotein and hCG are elevated, during screening for Down's syndrome, the possibility of a partial molar pregnancy with fetal malformation should be added to the differential diagnosis.

A voluminous paraovarian cyst. Case report.

Paraovarian cysts represent 9-10% of all annexial tumescences. The Authors present a case of voluminous paraovarian cyst in young woman referring abdominal heaviness and swelling for about eight months. During laparotomy a 35 cm cyst with liquid content was revealed. The cystic mass was extirpated preserving the woman's reproductive capacity.

A rare case of IUD tubal migration. Case report.

The Authors describe a rare case of IUD tubal migration. The uterine device had been inserted twelve years before. A hysteroscopical removal of the IUD was tried unsuccessfully, because it was impossible to locate it either in the uterine cavity or at the fallopian tube orifice level. The patient underwent a minilaparotomy and the IUD was found out at the peritubal level. An ecographic control of all intrauterine devices insertions is recommended.

Vaginal endometriosis. Two case reports and review of the literature on rare urogenital sites.

The authors present two rare cases of vaginal endometriosis. Moreover, the literature regarding other sites of low genital tract involvement is reviewed.

[The expansion of NK CD56+ cells with reduced cytotoxicity in a female patient with systemic sclerosis]. / Espansione delle cellule NK CD56+ con ridotta citotossicità in una paziente affetta da sclerosi sistemica.

An absolute and relative increase of circulating CD56+ (NKH1, Leu19) natural killer cells has been found in a patient with systemic sclerosis. The expanded natural killer cells exhibited reduced natural killer activity and antibody-dependent cell-mediated cytotoxicity. Furthermore, the limiting dilution analysis of spontaneous in vitro immunoglobulin synthesis demonstrated that the precursor frequency of immunoglobulin-secreting cells and the "single-hit" kinetics of the titration curve were similar to healthy controls, but strongly different from previously reported patients in whom CD16+NK cell subset was expanded. Thus, our findings might suggest that expanded CD56+ natural killer cells exhibit unique regulatory properties on B cell function in systemic sclerosis.

Transplantation in Italy.

Organ procurement and transplantation have been difficult in Italy for many years. However, recent initiatives at the organizational level led to the establishment of the National Reference Centre, which is working hard to accomplish its tasks. We describe the transplantation activity of the past 2 years, which shows an improved situation that is encouraging. We include a brief history on transplantation in Italy and give some information to enhance understanding of the changes that have occurred and their impact on transplantation.

Organ transplantation in Italy: analysis of donors and recipients.

The Istituto Superiore di Sanità (The Italian National Institute of Health) has been collecting information regarding organ donation and transplantation in Italy. Herein we describe organ procurement and transplant activity in Italy in the years 1992 1997 and show some of the characteristics regarding both donors and transplanted patients who received kidneys, hearts, livers and lungs. Although transplantation in Italy has been very difficult because of shortage of organ donors, national rates have been improving year after year. The present situation should ameliorate further to enable Italy to reach the same level of other advanced European countries.

Analysis of organ donation in Italy.

In 1995 the Italian Institute of Health began assembling information regarding organ donors, recipients, and transplants. Data on more than 3000 transplants were collected and recorded to date. In addition to characteristics of donors and donating hospitals, this article describes donation activity and organ procurement in Italy from 1992 to 1996. Despite the encouraging results, the donation situation in Italy remains a challenge due to the nonhomogeneous distribution of organ donation throughout the country. It is hoped that an increase in the rate of organ donation and procurement in some regions will enable Italy to reach the European mean.