In silico prediction and ex vivo evaluation of potential T-cell epitopes in glycoproteins 4 and 5 and nucleocapsid protein of genotype-I (European) of porcine reproductive and respiratory syndrome virus

T-cell epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) glycoproteins 4 (GP4), 5 (GP5) and nucleocapsid (N) were predicted using bioinformatics and later tested by IFN-γ ELISPOT in pigs immunized with either a modified live vaccine (MLV) or DNA (open reading frames 4, 5 or 7). For MLV-vaccinated pigs, immunodominant epitopes were found in N but T-epitopes were also found in GP4 and GP5. For DNA-immunized pigs, some peptides were differently recognized. Using a large set of PRRSV sequences it was shown that N contains a conserved epitope and that for GP5, the genotype-I counterparts of previously reported epitopes of genotype-II strains were also immunogenic.     

The role of natriuretic peptides in volume assessment and mortality prediction in Haemodialysis patients

Background

Maintaining optimal fluid balance is essential in haemodialysis (HD) patients but clinical evaluation remains problematic. Other technologies such as bioimpedance are emerging as valuable adjuncts. This study was undertaken to explore the potential utility of the natriuretic peptides – atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the assessment of fluid status and cardiovascular risk in this setting.

Methods

This was a cross-sectional study carried out in an unselected cohort of 170 prevalent HD patients. Volume status was assessed by clinical parameters – the presence or absence of peripheral oedema, raised jugular venous pressure and basal lung crepitations; by extracellular fluid volume (ECFV) status determined by whole body bioimpedance; and by serum levels of BNP and ANP (pre- and post –dialysis). The relationships of ANP and BNP levels to clinical and bioimpedance parameters of volume status was determined. Patients were followed up for 5 years to assess the relationship of natriuretic peptide levels to mortality.

Results

Bioimpedance estimates of ECFV expansion (>105 % of ideal ECFV) was present in 52 % of patients pre-dialysis. A significant proportion (21 %) of pre-dialysis patients had a depleted ECFV (<95 % of ideal ECFV) pre-dialysis. The situation was reversed post-dialysis. A raised JVP >3 cm was the most reliable clinical sign of ECFV expansion inferred from bioimpedance measurements and natriuretic peptide levels. The vast majority of patients with this sign also had lung crepitations or peripheral oedema or both. BNP was a stronger predictor of ECFV expansion than either pre- or post-dialysis ANP. BNP was also a stronger predictor of five-year survival.

Conclusion

Serum levels of BNP have a strong relationship to both volume status and survival in HD patients. We found no clear role for measurement of ANP, though changes in blood levels may be a sensitive indicator of acute changes in volume status. Whether monitoring levels of these peptides has a role in the management of volume status and cardiovascular risk requires further study.

     

Risk factors for positive findings in patients with high‐grade T1 bladder cancer treated with transurethral resection of bladder tumour (TUR) and bacille Calmette‐Guérin therapy and the decision for a repeat TUR

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To determine factors predictive of positive findings at the 3‐month follow‐up evaluation (after transurethral resection of bladder tumour [TUR] and bacille Calmette‐Guérin [BCG] therapy) in patients with initial high‐grade (HG)T1 bladder cancer, and to assess the depth of lamina propria (LP) invasion and effectiveness of BCG therapy.

PATIENTS AND METHODS

In all, 138 patients with initial HGT1‐transitional cell carcinoma (TCC) were prospectively assigned, after TUR + BCG and according to depth of LP invasion, to a postBCG‐TUR (T1b) or cystoscopy/cytology (T1a) at 3 months. Any finding at 3 months was considered positive. The predictive value of 11 clinical and pathological variables was assessed by chi‐squared, Mann–Whitney U and multivariate logistic regression.

RESULTS

Of the 138 patients (14 women, mean age 69 years), 42% had T1a and 58% T1b TCC. Tumour size and carcinoma in situ (CIS) were significantly associated with positive findings and present in 26% (36/138) of the patients. The postBCG‐TUR (T1b cases), was positive in 31% (25/80), including seven infiltrating tumours. On multivariate analysis, again a tumour size of >3 cm (odds ratio, OR, 7.02) and associated CIS (OR 5.4) were significantly related to a positive postBCG‐TUR. A secondary finding was that at 20.3 months; patients with T1a TCC, who did not undergo a repeat TUR, did not have increased progression; only 3% (two of 58) had progressed compared with 21% (17/80) of those with T1b/c TCC (P < 0.002).

CONCLUSIONS

In initial HGT1‐TCC, tumour size and CIS were predictive factors of positive findings at 3 months after the initial TUR + BCG therapy. Patients with HGT1‐TCC invading the LP (T1b TCC) had a seven times higher risk of a positive repeat TUR if the initial tumour was >3 cm and a five‐fold increased risk if associated with CIS. The repeat TUR after BCG therapy allowed confirmation of complete resection and pathological evaluation of the BCG response. Although data are still preliminary, the strategy of performing a repeat TUR only in cases with LP involvement, i.e. T1b TCC, did not increase the risk of progression in cases with T1a TCC.     

Complete regression of melanoma associated with vitiligo

A 53-year-old woman presented with vitiligo. A pigmented lesion was disclosed in the physical examination. Its histopathologic study showed the presence of a band of melanophages in an uneven distribution. Fibroplasia and telangiectasias were also observed, but neither nevus nor melanoma cells were found. A short time afterwards, the patient developed a metastasis in an inguinal lymph node. In spite of high-dose interferon treatment, the patient died two years after the diagnosis. This case associates two uncommon events: a) the whole regression of a melanoma and b) vitiligo associated with melanoma. Although both processes have a similar pathogenic mechanism, this association is exceptional and probably influences the prognosis.     

Predicting single and mixture toxicity of petrogenic polycyclic aromatic hydrocarbons to the copepod Oithona davisae

In the present study, the acute toxicity of 10 polycyclic aromatic hydrocarbons (PAHs) associated with the Prestige fuel oil spill (Spain, 2002) were evaluated, either as single substances or in mixtures, in adults of the copepod Oithona davisae. All but dimethylphenanthrene had negative effects on O. davisae survival at concentrations below their water solubility, with 48-h median lethal concentrations for naphthalene and pyrene of 56.1 and 0.8 micromol/L, respectively, making these the least and most toxic compounds. Polycyclic aromatic hydrocarbons had narcotic effects on copepods, as evidenced by the lack of motility at lower concentrations than those causing death. Naphthalene showed the greatest narcotic effects, and phenanthrene showed minor effects. Acute toxicity of the tested PAHs was inversely related (r2 = 0.9) with their octanol-water partition coefficient, thereby confirming the validity of the baseline quantitative structure-activity regression models for predicting the toxicity of PAH compounds in copepod species. When supplied in mixtures, the toxic effect of PAHs was additive. These results indicate that the many PAHs in an oil spill can be considered unambiguous baseline toxicants (class 1) acting additively as nonpolar narcotics in copepods; hence, their individual and combined toxicity can be predicted using their octanol-water partition coefficient.