Anti-V3 and anti-IgG antibodies of healthy individuals share complementarity structures.

It was recently shown that antibodies reactive with a peptide from the tip of the HIV-1NY5 gp120 V3 loop (V3 peptide) are present not only in sera of HIV-positive patients but also in sera of healthy HIV-negative individuals. In the present study, we show that V3 peptide reactive antibodies are predominantly IgM in sera of HIV negative individuals and that a fraction of the IgG anti-V3 antibodies exhibit features of autoantibodies. These antibodies were purified by chromatography on IgG-sepharose columns from sera as well as from purified IgG anti-V3 antibodies. A higher IgG anti-V3 reactivity was detected in autoantibody preparations from HIV-positive sera as compared with the reactivity of sera and purified antibodies from HIV-negative individuals. This was confirmed by solid phase binding of IgG anti-V3 antibodies both to V3 and to human IgG F(ab')2 antigens. The autoantibodies did not bind to peptides that share sequence similarity with V3 peptide indicating a high epitope specificity. The detection of antibodies against HIV epitopes in HIV-negative individuals may suggest that anti-V3 antibodies after HIV infection represent at least in part a secondary immune response.     

Molecular makeup of HIV-1 envelope protein

A broad range of structural, functional, and immunological similarities between HIV-1 gp120 and human proteins, especially those participating in immune responses, highlight gp120 as a pleiotropic protein that can in different ways affect many important functions of the human immune system. Here we described some of these properties of HIV-1 gp120 that represent the main obstacle in the development of effective and safe AIDS vaccine.     

Application of VIP/NTM-reactive natural antibodies in therapy of HIV disease

In sera of HIV-infected individuals natural antibodies recognizing nonimmunogenic C-terminal domain of the second conserved region of HIV-1 gp120 and the vasoactive intestinal peptide (VIP) were identified. It has been demonstrated that these antibodies are significantly more prevalent in asymptomatic carriers than in AIDS patients and that their titer strongly correlates with disease progression. These findings point out the VIP/C2-reactive natural antibodies as an important agent for immunotherapy of HIV disease.     

Long-term follow-up and prognosis of chronic granulomatous disease in Yugoslavia: is there a role for early bone marrow transplantation?

We report the long-term follow-up of 12 pediatric-aged patients with chronic granulomatous disease (CGD). The mean age at the onset of infections was 5 months with a median delay in diagnosis of 2.5 years. Bacille Calmette–Guérin lymphadenitis was the most common presenting infection (6) followed by suppurative lymphadenitis (4), liver abscess (1), or Salmonella sepsis (1). Prophylaxis with cotrimoxazole was recommended to all patients. During the mean follow-up of 10 years (range, 4–23 years) pneumonitis was the most prevalent infection (91%) followed by lymphadenitis (83%), aphtous stomatitis (58%), and liver abscesses (25%). Seven (58%) patients developed chronic lung disease due to grossly delayed diagnosis (3) or poor compliance with antimicrobial prophylaxis (4). Five (41%) patients died during the second decade of life of aspergillosis (3) or chronic lung disease (2). Probability of survival into the third decade of life was estimated to be only 19%. We argue that HLA-identical bone marrow transplantation (BMT), if possible, should be attempted at early age because of significant morbidity and mortality in adolescence. BMT also should be considered in patients who suffer severe infections despite antimicrobial prophylaxis or patients with evidence of chronic lung disease. Possibility of elective BMT from unrelated donors remains to be carefully evaluated.     

The presence of antibodies recognizing a peptide derived from the second conserved region of HIV-1 gp120 correlates with non-progressive HIV infection

The C-terminus of the second conserved region of HIV-1 gp120 represents a functionally important domain, as it encompasses amino acids directly involved in the binding to the CD4 receptor and in post-receptor binding events. Previous studies have suggested that antibodies with specific affinity to a 23 amino acids-long NTM polypeptide, derived from this HIV-1 gp120 domain, may be involved in the control of HIV disease progression. In the current work, we searched for NTM-recognizing antibodies in specific cohorts of HIV-1 infected individuals, including long-term nonprogressors (LTNP) and progressors. For this purpose, we employed a previously defined bioinformatics criterion for design of an NTM peptide mimetic to select an octapeptide, NTMs (FTDNAKTI), which is more suitable for use in a solid-state enzyme-linked immunosorbent assay (ELISA). Our results show that NTMs-reactive antibodies are significantly more prevalent (p < 0.01) in LTNP as compared to progressors and healthy control subjects, indicating their association with non-progressive infection. The presence of antibodies recognizing the second conserved region of the HIV-1 gp120 derived peptide, NTMs, in LTNP sera suggest that these antibodies could be of considerable interest for development of anti-HIV immune-based therapies and vaccines.     

Beneficial effects of calcium oral coadministration in gentamicin-induced nephrotoxicity in rats

Frequent therapeutical use of an aminoglycoside antibiotic gentamicin (GM) is limited by its nephrotoxic effects often characterized by both morphological and functional alterations of kidney leading to acute renal failure. The aim of this study was to examine the effect of dietary calcium supplementation on GM-induced nephrotoxicity in rats. Experiments were performed on 30 adult male Wistar rats divided into three groups of 10 animals each. G-group received GM intraperitoneally at a dose of 100 mg/kg; GCa-group received the same dose of GM concomitantly with 1 g/kg calcium carbonate given orally; and C-group, serving as control, received 1 mL/day of normal saline. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural and functional changes of kidney was performed by histopathological, morphometrical, and biochemical analyses. Compared with control, G-group of rats were found to have diffusely and unequally thickened glomerular basement membrane with neutrophil cells infiltration. In addition, vacuolization of cytoplasm of proximal tubule cells with coagulation-type necrosis was observed. These GM-induced pathological lesions were significantly reduced in the rats of GCa-group. Morphometric analysis revealed statistically significant differences in the size of glomeruli (area, major and minor axes, perimeter), optical density, and roundness of glomeruli (p < 0.05) between G and GCa groups. Biochemical analysis showed significant elevation in blood urea and serum creatinine concentrations, whereas potassium concentration was lowered in G-group compared with the other groups (p < 0.01). It is concluded that oral supplementation of calcium during treatment with GM resulted in significant reduction of morphological and functional kidney alterations.     

Neurophysiological effects of mistletoe (Viscum album L.) on isolated rat intestines

Mistletoe (Viscum album L.) is well known as a medicine from ancient times and the earliest notes. Today it is used as a remedy. The aim of this research was to examine the effects of mistletoe extracts and their components on some neurophysiological parameters in rat intestines. The tonus and contractile responses of isolated intestinal segments (duodenum, ileum and distal colon) were analysed. The experiment was carried out in three groups. In the first group (control group) different concentrations of acetylcholine were added into the organ bath (10-50 nmol/L). In the second group, mistletoe extracts were added into the organ bath with increasing concentrations and in the third group, atropine, a non-selective muscarinic receptor antagonist, was added into the organ bath (concentration 10(-7) mol/L) and after atropine plant extracts were administered. The results obtained suggest that extracts from different parts of mistletoe have neurophysiological effects and change intestinal contractions. The results also suggest that the effects of mistletoe extracts on intestinal contractility act via cholinergic pathways, activating muscarinic receptors in the intestines. However, in order to establish the subtype of receptors, further investigations are necessary where selective antagonists of muscarinic cholinergic receptors should be used.