Global risk stratification in primary hypertension: the role of the kidney

OBJECTIVE: Microalbuminuria and a reduction in creatinine clearance are well known, independent predictors of unfavourable cardiovascular prognosis. Our aim was to evaluate the impact of renal damage on global risk stratification in 459 non-diabetic, untreated hypertensive patients (64% men, mean age 47.3 years). METHODS: Renal damage was defined as creatinine clearance < 60 ml/min per 1.73 m2 (Cockcroft-Gault formula) or the presence of microalbuminuria (albumin to creatinine ratio). Cardiac and vascular organ damage was assessed by ultrasound scan. We evaluated the impact of renal damage, left ventricular hypertrophy and carotid atherosclerosis on risk stratification as recommended by the 2007 European Society of Hypertension-European Society of Cardiology Guidelines. RESULTS: The prevalence of renal damage, microalbuminuria and creatinine clearance < 60 ml/min per 1.73 m2 was 24, 12 and 13%, respectively. There was no correlation between albuminuria and estimated creatinine clearance, and only 0.9% of patients showed microalbuminuria and reduced creatinine clearance simultaneously. The presence of renal damage entailed a 3.3 times higher risk of having cardiovascular abnormalities. Based on routine work-up, 58% of our study patients were classified as high-very high risk. The simultaneous evaluation of albuminuria and creatinine clearance resulted in a significant change in risk stratification, since 68% of patients were classified in the high-very high risk class. The search for left ventricular hypertrophy or carotid atherosclerosis by ultrasonography did not improve risk stratification significantly as compared to the assessment of renal damage. CONCLUSIONS: Our findings support the assessment of renal abnormalities as the first step when evaluating target organ damage for cardiovascular risk assessment in hypertensive patients.     

A novel vehicle for the treatment of psoriasis

This study evaluates the effectiveness of the topical use of an aerosol foam combination of calcipotriol 50 μg/g plus betamethasone dipropionate 0.5 mg/g (Cal/BD foam, Enstilar®) in adults with moderate plaque psoriasis. A total of 120 male and female adult psoriasis patients (53.3% male) from two Italian dermatological units were enrolled in an 8‐week prospective study performed between November 2018 and January 2019. Psoriasis Area and Severity Index (PASI) was evaluated at baseline (T0) and 4 weeks (T4) of daily application, and a further evaluation was carried out 4 weeks after suspension (T8). Furthermore, the Dermatology Life Quality Index (DLQI) was evaluated at baseline and after 4 weeks of treatment (T4). At baseline, patients presented a mean PASI of 7 (7.0 ± 2.1). After 4 weeks (T4) of once‐daily application, an important improvement in PASI was observed (1.1 ± 0.3). At Week 4, DLQI was reduced by 5.5 points from baseline (mean: 12 ± 3.1 at T0 vs 6.5 ± 1.8 at T4). Four weeks after suspension (T8), mean PASI was 2.6 ± 1.9, which was stable compared to the previous evaluation; only 8.3% of the treated patients showed worsening of plaque psoriasis. This study suggested that the Cal/BD aerosol foam is an effective topical therapy to treat plaque psoriasis.     

Amoxicillin-clavulanic acid versus cefotaxime in the therapy of bacterial infections in cirrhotic patients

BACKGROUND/AIM: Cefotaxime is considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing bacterial infections. It has been suggested that amoxicillin-clavulanic acid could be an alternative to cefotaxime, particularly in patients developing bacterial infections while on prophylactic norfloxacin. The aim of the present study was to compare amoxicillin-clavulanic acid with cefotaxime in the treatment of bacterial infections in cirrhosis. METHODS: Ninety-six hospitalized cirrhotic patients with suspicion of bacterial infection were prospectively included and randomized into two groups: one group (n=48) received amoxicillin-clavulanic acid, first intravenously 1 g-0.2 g every 8 h, and then orally 500 mg-125 mg every 8 h, and the other group (n=48) received intravenous cefotaxime 1 g every 6 h. Patients were stratified for previous prophylaxis with norfloxacin and ascitic fluid infection. RESULTS: Sixteen patients were excluded from the analysis because bacterial infection was not demonstrated or because of secondary peritonitis. Therefore, 38 patients from the amoxicillin-clavulanic acid group and 42 from the cefotaxime group were finally analyzed. There were 24 ascitic fluid infections in each group. Infection resolution (86.8% vs 88%, 95% CI: -0.15 to 0.13, p NS), spontaneous bacterial peritonitis resolution (87.5% vs 83.3%, 95% CI: -0.15 to 0.24, p NS), duration of treatment, incidence of complications, time of hospitalization and hospital mortality were similar in both groups. Considering patients on prophylactic norfloxacin, infection resolution was also similar (100% vs 83.3%, 95% CI: -0.04 to 0.37, p NS). No adverse events were observed in either of the two groups. The cost of antibiotics was statistically lower in the amoxicillin-clavulanic acid group (p<0.001). CONCLUSIONS: Amoxicillin-clavulanic acid is as effective as cefotaxime in the treatment of bacterial infections in cirrhotic patients, but is less expensive and can be administered orally. These results suggest that amoxicillin-clavulanic acid is an effective alternative to cefotaxime for the empirical treatment of bacterial infections in cirrhosis.     

Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44

Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion.     

Biological response of human bone marrow mesenchymal stem cells to fluoride‐modified titanium surfaces

Objectives: The aim of the present study was to examine the behaviour of human bone marrow‐derived mesenchymal stem cells (BM‐MSC) to fluoride‐modified grit‐blasted (F‐TiO) titanium surfaces compared with grit‐blasted ones (TiO). Material and methods: Implant surfaces were analysed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). BM‐MSC were isolated from healthy donors and grown on the implant surfaces. Cell adhesion and proliferation, type I collagen (Col I) synthesis, osteoblastic differentiation (in terms of alkaline phosphatase activity, osteocalcin synthesis and extracellular matrix mineralization) were assessed. Furthermore, the ability to affect the osteoblastic/osteoclastic balance in terms of osteoprotegerin (OPG) and activator of nuclear factor κ B ligand (RANKL) ratio was investigated. Results: F‐TiO surface showed higher S_a values (P<0.05) and the presence of nano‐scale structures at the AFM and SEM analysis. Comparable cell morphology and similar adhesion values on both surfaces were detected at early time, whereas higher proliferation values on F‐TiO samples were observed at 7 and 10 days. Increased Col I and OPG levels for cells grown on F‐TiO were found, whereas RANKL was not detectable in any of the conditioned media. BM‐MSC showed a similar expression of early and late osteogenic markers on both TiO and F‐TiO surfaces. Conclusions: The results of the present study show that the chemical and micro/nano‐scale modifications induced by fluoride treatment of TiO‐grit blasted surfaces stimulate the proliferation and the extracellular matrix synthesis by BM‐MSC, as well as the increase of OPG synthesis, thus preventing osteoclast activation and differentiation. To cite this article:
Guida L, Annunziata M, Rocci A, Contaldo M, Rullo R, Oliva A. Biological response of human bone marrow mesenchymal stem cells to fluoride‐modified titanium surfaces.
Clin. Oral Impl. Res. 21 , 2010; 1234–1241.
doi: 10.1111/j.1600‐0501.2010.01929.x     

Chronic pain in urological diseases: a clinical review

Chronic pain is the central problem in a variety of urological diseases. Pain is an unpleasant sensory and emotional experience associated with either actual or potential tissue damage, or described in terms of such damage. The aim of this research was to update knowledge about the ultrastructural, clinical, psychological and therapeutic aspects of chronic pain in urological diseases, in particular in chronic pelvic syndrome. In this paper we have revisited the most significant and discussed articles published in the last twenty five years, with particular references on the 2008 European Guidelines, searching key words (chronic pelvic pain syndrome, chronic pelvic pain, chronic prostatitis, interstitial cystitis, prostatodynia, urological disease) and data with a high level of evidence. The articles that we have analyzed show that pain is characterized by an initial tissue injury that can lead to sensitization, which is a decrease in the intensity of the stimulus needed to elicit a response by the nerve, involving the peripheral and central nervous systems. The chronic pain state is characterized by loss of inhibitory interneurons, establishment of aberrant excitatory synaptic connections and long-term potentiation of response due to changes in sensitivity of nerve synapses. Stress and hormones might also play a role in central sensitization. Pain also has a cognitive and emotional component. It is very difficult to treat, given the complex nature of the response and the interaction of physiological aspects     

Expression of protectin (CD59) in human melanoma and its functional role in cell- and complement-mediated cytotoxicity

Immunohistochemical and/or indirect immunofluorescence analysis with monoclonal antibody (MAb) H19 demonstrated the expression of protectin (CD59) in 54 surgically removed metastatic melanoma lesions and on 8 out of 12 melanoma cell lines. CD59 expression had a low degree of intra- and intertumor heterogeneity. SDS-PAGE analysis showed that the molecular weight of CD59 expressed on melanoma cells is about 20 kDa. Treatment of melanoma cells with 5 U/ml of phosphatidylinositol-specific phospholipase C completely abolished cell-surface expression of CD59. Interferon-γ and/or tumor necrosis factor-α or phorbol 12-myristate 13-acetate neither modulated the expression of CD59 by melanoma cells nor influenced the amounts of CD59-specific mRNA. F(ab')₂ fragments of anti-CD59 MAb YTH53.1 did not inhibit the lysis of melanoma cells by allogeneic natural killer (NK) cells or lymphokine-activated killer (LAK) cells. In contrast, the whole lg molecule of MAb H19 or YTH53. I significantly (p < 0.05) enhanced NK-cell-mediated lysis of melanoma cells, suggesting the induction of antibody-dependent cell-mediated cytotoxicity. Lastly, masking of CD59 by MAb YTH53. I or its F(ab')₂ fragments significantly (p < 0.05) enhanced, in a dose-dependent fashion, the lysis of anti-GD3-sensitized melanoma cells by homologous complement. These data demonstrate that CD59 expressed by human melanoma cells might regulate host-tumor interaction by protecting neoplastic cells from complement-mediated lysis. © 1995 Wiley-Liss, Inc.     

A case of primary toxoplasmosis in an immunocompetent patient

CASE REPORT: A case of an immunocompetent patient presenting primary systemic toxoplasma infection involving the eye (condition seen in less than 3% of primary infections). The patient showed reactivation of this primary focus two years later. DISCUSSION: Diagnosis of toxoplasm retinitis is based on a typical lesion consisting in an area of active retinitis adjacent to an inactive corioretinal scar. Differential diagnosis must consider other causes of retinal coroiditis in primary infection cases: sarcoidosis, tuberculosis, syphilis as well as viral and fungal infections. Ocular toxoplasmosis was confirmed by serum tests.