Kidney post-transplant monitoring of urinary glycosaminoglycans/proteoglycans and monokine induced by IFN-γ (MIG)

Allograft rejection during the first year after renal transplantation can lead to persistent allograft dysfunction and reduced long-term graft survival. Thus, it is important to define early predictors of kidney damage, less invasive than allograft biopsy. Urinary glycosaminoglycan/proteoglycan concentration and distribution, N-acetyl-β-(d)-glucosaminidase (NAG), and monokine induced by IFN-γ (MIG) levels were evaluated in the immediate post-transplant and during a 1-year follow-up. We observed increased urinary levels of MIG, urinary trypsin inhibitor and its degradation products, the lack of urinary heparan sulfate excretion, and the decreased chondroitin sulfate relative content at day 1 post-transplant in most patients who developed complications in the postoperative period. Moreover, urinary MIG levels showed significant correlations with NAG, C-reactive protein, and GFR at day 1 post-transplant. The monitoring of glycosaminoglycan/proteoglycan urinary pattern and the levels of urine MIG could serve as useful markers for predicting possible complications of transplantation, unraveling an early inflammatory state, on whose basis the immunosuppressive therapy could be appropriately modified.     

Short-term variations in bone remodeling markers of an oral contraception formulation containing 3 mg of drospirenone plus 30 microg of ethinyl estradiol: observational study in young postadolescent women

The clinical study of treated subjects and nontreated controls was made in healthy eumenorrheic young postadolescent women volunteers in the Department of Obstetrics and Gynaecology at Cagliari University, to investigate whether an oral contraceptive (OC) containing drospirenone (3 mg) plus ethinyl estradiol (30 microg) (DRSP+EE) can affect bone metabolism. Control group (n = 26) and OC group (n = 28) women did not differ in age, body mass index, waist-to-hip ratio and main outcome measures [urinary levels of deoxypyridinoline and pyridinoline, serum levels of osteocalcin, bone specific alkaline phosphatase (bSAP), total testosterone (total-T), sex hormone-binding globulin (SHBG), progesterone and bone mineral density (BMD) at the heel]. The control group was studied at the luteal phase (LP) during both the first and the sixth menstrual cycle; the OC group was studied during the first cycle at the LP, and on days 16-18 of the sixth cycle of DRSP+EE treatment. At the sixth cycle, in the control group, the main outcome measures did not change compared to baseline. In the OC group, deoxypyridinoline, pyridinoline, osteocalcin, bSAP, total-T and progesterone levels were reduced, whereas SHBG levels were increased. The BMD was unchanged compared to baseline. The results suggest that 6-month DRSP+EE treatment decreases bone turnover.     

Levels of S100B protein are higher in mature human milk than in colostrum and milk-formulae milks

BACKGROUND & AIMS: Human milk is believed to contain biological factors involved in the regulation of newborn growth, including brain development. Recently, it has also been shown to contain the calcium-binding S100B protein, regarded as a neurotrophic factor. The present study investigates the concentrations of this protein in colostrum, human milk at different levels of maturation and in milk-formulae.METHODS: Samples for S100B measurements were collected from human colostrum (on day 1 after birth), from transition milk (on post-delivery days 7 and 14) and from mature milk (on day 30 after delivery) in 14 healthy women and from 14 milk-formulae. The S100B protein levels were measured using a commercially available specific immunoluminometric assay. RESULTS: Mean S100B protein levels were significantly higher in mature human milk (117.9+/-36.7 microg/l) than in transition milk at 14 days (106.7+/-38.1 microg/l) and at 7 days (92.7+/-37.8 microg/l), colostrum (74.6+/-37.6 microg/l) or milk-formulae (24.8+/-19.5 microg/l) (P<0.001, for all). A correlation between human milk S100B levels and the gestational age at which samples were obtained was also found (r=0.39; P<0.01).CONCLUSIONS: These findings, possibly related to S100B's neurotrophic role, offers useful information to the investigation of the role of S100B protein in brain maturation.     

Constitutive expression of HIV-VLPs in stably transfected insect cell line for efficient delivery system

We have previously developed HIV-1 Pr55gag-based virus-like particles (HIV-VLPs) as presentation and delivery model using a transient Baculovirus expression system. Here we describe the establishment and characterization of stably transfected insect cell line for the constitutive and reproducible production of HIV-VLPs. The persistence of HIV gag coding gene has been verified in clonal resistant insect cells and the protein expression has been confirmed by Western blot analysis. The resulting HIV-VLPs have been evaluated by standard transmission electron microscopy and their immunogenicity has been evaluated in vivo. Our results demonstrate that this strategy is highly efficient for constitutive expression of conformational enveloped VLPs which can be employed as presentation and delivery system for pathogen as well as tumor-associated antigens. This represents, to our knowledge, the first example of stably transfected insect cell line for the constitutive production of VLPs.     

Case report 590

The authors present the case of a patient 54 years of age who developed well-defined osteolysis in the distal end of the humerus, with a slight radiodensity in the soft tissue. The radionuclide scintigram and above all the CT, were useful in defining the characteristics and expansion of the mass more precisely. Surgical intervention and histological examination demonstrated a seemingly unique case of PVNS of the elbow with diffuse cartilaginous components and erosion of the distal end of the humerus. The pathological findings in this unusual case, actually suggested the possibility of an intermediate form of PVNS associated with synovial chondromatosis.     

Impact of positive end-expiratory pressure on the definition of acute respiratory distress syndrome

Objective We examined whether PEEP during the first hours of ARDS can induce such a change in oxygenation that could mask fulfillment of the AECC criteria of a PaO₂/FIO₂ 200 essential for ARDS diagnosis.Design and setting Observational, prospective cohort in two medical-surgical ICU in teaching hospitals.Patients 48 consecutive patients who met AECC criteria of ARDS on 0 PEEP (ZEEP) at the moment of diagnosis.Measurements and results PaO₂/FIO₂ and lung mechanics were recorded on admission (0 h) to the ICU on ZEEP, and after 6, 12, and 24 h on PEEP levels selected by attending physicians. Lung Injury Score (LIS) was calculated at 0 and 24 h. PaO₂/FIO₂ rose significantly from 121±45 on ZEEP at 0 h, to 234±85 on PEEP of 12.8±3.7 cmH₂O after 24 h. LIS did not change significantly (2.34±0.53 vs. 2.42±0.62). These variables behaved similarly in pulmonary and extrapulmonary ARDS, and in survivors and nonsurvivors. After 24 h only 18 patients (38%) still had a PaO₂/FIO₂ of 200 or lower. Their mortality was similar to that in the remaining patients (61% vs. 53%).Conclusions The use of PEEP improved oxygenation such that one-half of patients after 6 h, and most after 24 h did not fulfill AECC hypoxemia criteria of ARDS. However, LIS remained stable in the overall series. These results suggest that PEEP level should be taken into consideration for ARDS diagnosis.     

The use of immune complex vaccines to enhance antibody responses against neutralizing epitopes on HIV-1 envelope gp120

The capacity of immune complexes to augment antibody (Ab) responses is well established. The enhancing effects of immune complexes have been attributed mainly to Fc-mediated adjuvant activity, while the ability of Abs to induce antigenic alterations of specific epitopes as a result of immune complex formation has been less well studied. Previously we have shown that the interaction of anti-CD4-binding site (CD4bs) Abs with HIV-1 gp120 induces conformation changes that lead to enhanced antigenicity and immunogenicity of neutralizing epitopes in the V3 loop. The present study shows that significant increases in the antigenicity of the V3 and C1 regions of gp120 were attained for several subtype B gp120s and a subtype C gp120 upon immune complex formation with the anti-CD4bs monoclonal Ab (mAb) 654-D. Such enhancement was observed with immune complexes made with other anti-CD4bs mAbs and anti-V2 mAbs, but not with anti-C2 mAbs, indicating this activity is determined by antigen specificity of the mAb that formed the immune complex. When immune complexes of gp120_LAI/654-D and gp120_JRFL/654-D were tested as immunogens in mice, serum Abs to gp120 and V3 were generated at significantly higher titers than those induced by the respective uncomplexed gp120s. Notably, the anti-V3 Ab responses had distinct fine specificities; gp120_JRFL/654-D stimulated more cross-reactive anti-V3 Abs than gp120_LAI/654-D. Neutralizing activities against viruses with heterologous envelope were also detected in sera of mice immunized with gp120_JRFL/654-D, although the neutralization breadth was still limited. Overall this study shows the potential use of gp120/Ab complexes to augment the immunogenicity of HIV-1 envelope gp120, but further improvements are needed to elicit virus-neutralizing Ab responses with higher potency and breadth.     

Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy

Purpose: Seizure exacerbation in catamenial epilepsy (CE) is associated with the decrease in progesterone secretion and increase in estradiol secretion during the premenstrual period. Moreover, experimental evidence suggests that tetrahydrodeoxycorticosterone (THDOC), a positive modulator of the type A receptor for γ-aminobutyric acid (GABA), and dehydroepiandrosterone sulfate (DHEAS), a negative modulator of this receptor, might play a crucial role in modulating seizure frequency during the menstrual cycle. Following these studies it seems of interest to investigate possible variations, among other hormonal parameters, of THDOC and DHEAS in CE patients.
Methods: The serum concentrations of progesterone (P4), pregnenolone, allopregnanolone (AP), THDOC, DHEAS, cortisol, and DHEAS/cortisol ratio were measured throughout the menstrual cycle at the 7th, 11th, 15th, 19th, 23rd, and 27th day from the onset of spontaneous menstrual blood loss in young premenopausal women with CE (n = 17) and age-matched controls (n = 13).
Results: At each time of the study, the serum concentration of THDOC and the DHEAS/cortisol ratio were lower (p < 0.05) in women with CE than in control women. The concentrations of P4, pregnenolone, and AP did not differ between the two groups of subjects.
Conclusions: The reduced serum concentration of THDOC and the reduced DHEAS/cortisol ratio detected throughout the menstrual cycle in women with CE might play a role in CE. Moreover, the peculiar pattern of CE seizure exacerbation might suggest that these neuroendocrine variations are worth investigating in other epileptic syndromes, particularly in those characterized by relevant and uncontrolled variations in seizure frequency.