Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects

Salt-losing tubulopathies with secondary hyperaldosteronism (SLT) comprise a set of well-defined inherited tubular disorders. Two segments along the distal nephron are primarily involved in the pathogenesis of SLTs: the thick ascending limb of Henle’s loop, and the distal convoluted tubule (DCT). The functions of these pre- and postmacula densa segments are quite distinct, and this has a major impact on the clinical presentation of loop and DCT disorders – the Bartter- and Gitelman-like syndromes. Defects in the water-impermeable thick ascending limb, with its greater salt reabsorption capacity, lead to major salt and water losses similar to the effect of loop diuretics. In contrast, defects in the DCT, with its minor capacity of salt reabsorption and its crucial role in fine-tuning of urinary calcium and magnesium excretion, provoke more chronic solute imbalances similar to the effects of chronic treatment with thiazides. The most severe disorder is a combination of a loop and DCT disorder similar to the enhanced diuretic effect of a co-medication of loop diuretics with thiazides. Besides salt and water supplementation, prostaglandin E2-synthase inhibition is the most effective therapeutic option in polyuric loop disorders (e.g., pure furosemide and mixed furosemide–amiloride type), especially in preterm infants with severe volume depletion. In DCT disorders (e.g., pure thiazide and mixed thiazide–furosemide type), renin–angiotensin–aldosterone system (RAAS) blockers might be indicated after salt, potassium, and magnesium supplementation are deemed insufficient. It appears that in most patients with SLT, a combination of solute supplementation with some drug treatment (e.g., indomethacin) is needed for a lifetime

Gene expression and genotoxicity in Manila clam (Ruditapes philippinarum) modulated by sediment contamination and lagoon dynamics in the Po river delta

The lagoons of the Po River delta are potentially exposed to complex mixtures of contaminants, nevertheless, there is a substantial lack of information about the biological effects of these contaminants in the Po delta lagoons. These environments are highly dynamic and the interactions between chemical and environmental stressors could prevent the proper identification of biological effects and their causes. In this study, we aimed to disentangle such interactions focusing on Manila clams, previously exposed to six lagoons of the Po delta, adopting three complementary tools: a) the detailed description via modelling techniques of lagoon dynamics for salinity and water temperature; b) the response sensitivity of a number of target genes (ahr, cyp4, \u3c1-gst, \u3c3-gst, hsp22, hsp70, hsp90, ikb, dbh, ach, cat, Mn-sod, Cu/Zn-sod, cyp-a, flp, grx, TrxP) investigated in clam digestive glands by Real Time PCR; and c) the relevance of DNA adducts determined in clams as markers of exposure to genotoxic chemicals. The lagoons showed specific dynamics, and two of them (Marinetta and Canarin) could induce osmotic stress. A group of genes (ahr, cyp4, Mn-sod, \u3c3-gst, hsp-22, cyp-a, TrxP) seemed to be associated with overall lagoon characteristics as may be described by salinity and its variations. Lagoon modelling and a second group of genes (hsp70, hsp90, cat, ikb, ach, grx, Cu/Zn-sod) also suggested that moderate increases of river discharge may imply worse exposure conditions. Oxidative stress seemed to be associated with such events but it was slightly evident also under normal exposure conditions. DNA adduct formation was mainly associated with overwhelmed antioxidant defences (e.g. low Cu/Zn-sod) or seemingly with their lack of response in due time. In Po delta lagoons, Manila clam can be affected by chemical and environmental factors which can contribute to induce oxidative stress, DNA adduct formation and, ultimately, to affect clam condition and health

PReferentially Expressed Antigen in MElanoma (PRAME): preliminary communication on a translational tool able to early detect Oral Malignant Melanoma (OMM)

Oral malignant melanoma (OMM) has a prevalence less than 1% of all melanomas and it commonly develops on the oral mucosa following a slow and unspecific transformation of unstable melanocytic lesions, often resulting in a diagnostic delay. The marker PReferentially Expressed Antigen in MElanoma (PRAME) seems to be a valid tool to investigate the biological and histological nature of cutaneous melanocytic lesions, but to date its use to characterize pigmented lesions in the oral cavity is largely unexplored. The aim of this study was to create preliminary knowledge on the PRAME expression in OMM, and to compare its expression respect to other dysplastic pigmented lesions of the oral cavity. Interestingly, PRAME has been demonstrated to be reliable in the clinical conditions investigated in our pilot study; in fact, it has clearly differentiated the cases of Melanoma, which showed diffuse and intense positivity (score 6+/7+) to PRAME, from the other melanocytic nevi, which resulted to be mainly negative to PRAME. This means a better differential diagnosis, a reliable early diagnosis and a proper clinical/surgical management of the oncological lesions. In conclusion, PRAME can be a valid qualitative marker for differential diagnosis, not only in cutaneous melanomas, but also in malignant melanoma of the entire head and neck area

B cell clonality in gastric lymphoid tissues of patients with Sjogren's syndrome

Objective-To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjogren's syndrome (SS). Methods-Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement. Results-Organised MALT was found in of the patients, compared with of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality. Conclusion-Lymphoid accumulation in the gastric mucosa is common in Sjogren's syndrome, but full evidence for Department of an antigen driven B cell expansion could Pathology not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa