Optimization strategies for HIV, hepatitis and syphilis testing in Infectious Disease Clinic and Dermatology Unit of Modena: 7-year results of collaboration experience.

BACKGROUND: Screening tests for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis infections performed in at-risk population show a higher number of positive tests compared to those carried out in the general population. 'Test & Counselling' Ambulatory of Infectious Disease Clinic (T&C-IDC) and Sexually Transmitted Diseases Ambulatory of Dermatology Unit (STDs-DU) of Modena began collaboration in 2010 and adopted a common diagnostic serological profile since 2013. OBJECTIVES: The main objective was to analyse the number of screening tests performed in the T&C-IDC and STDs-DU, comparing the results obtained after the adoption of the shared protocol with the previous period. The secondary aim was to evaluate the linkage to care of newly diagnosed patients. METHODS: Consecutive patients referred to the T&C-IDC and STDs-DU from January 2010 to December 2016, with at least one performed screening test for HIV, HBV, HCV and syphilis were enrolled. Referral of patients with a new infection was obtained by capture-recapture methods in hospital databases. RESULTS: During the 7-year observation, we collected 13 117 admittances for 9154 patients. A significant increase in the number of screening tests (P < 0.001) and ratio between tests and admissions (P = 0.002) was observed. A total of 644 (7.0%) people with at least one infection were diagnosed. Among these, the most common was syphilis (41.9%), followed by HBV (25.7%), HCV (21.4%) and HIV (10.9%). Syphilis occurred predominantly in Italians (72.5%) and males (75.7%), as like as HCV, while foreign-born (85.5%) mainly harboured HBV infection. HIV diagnosis was detected more frequently among males (67.1%) with a similar proportion between Italians and foreign-born. Five hundred and forty-three out of 644 (84.3%) patients were linked to care. CONCLUSION: The collaboration between T&C-IDC and STDs-DU has proven to work well increasing the diagnosis over the time and obtaining good results in linkage to care.

Diazoxide postconditioning induces mitochondrial protein S-nitrosylation and a redox-sensitive mitochondrial phosphorylation/translocation of RISK elements: no role for SAFE.

Postconditioning (PostC) can be obtained either with brief cycles of ischemia/reperfusion (I-PostC) or with a direct targeting of mitochondria with Diazoxide (pharmacological PostC, P-PostC). I-PostC may induce the activation of RISK and SAFE pathways and may favor nitric oxide production with S-Nitrosylation of proteins and redox signaling. It is not clear whether Diazoxide can lead to similar effects. We compared the effects of I-PostC and P-PostC on (a) kinases of RISK- and SAFE pathway, (b) S-Nitrosylation of mitochondrial proteins and (c) reduction of death signals (PKCδ, cleaved caspase-3 and Beclin-1) in cytosolic and mitochondrial fractions. Isolated rat hearts underwent (1) perfusion without ischemia (Sham), (2) ischemia/reperfusion (30-min ischemia plus 2-h reperfusion), (3) I-PostC (5 intermittent cycles of 10-s reperfusion and 10-s ischemia immediately after the 30-min ischemia), (4) P-PostC (Diazoxide 30 µM in the first of 3-min of reperfusion) or (5) I-PostC + MPG or P-PostC + MPG (MPG, 2-mercaptopropionylglycine 300 µM). Using Western blot and biotin switch assay, we found that P-PostC induced a redox sensible phosphorylation/translocation of Akt, ERK1/2 and GSK3ß into the mitochondria, but not of phospho-STAT3, which was translocated into the mitochondria by I-PostC only. Either I-PostC or P-PostC increased mitochondrial S-Nitrosylated proteins (e.g., VDAC) and reduced the levels of phospho-PKCδ, cleaved caspase-3 and Beclin-1. Therefore, direct targeting of mitochondria with Diazoxide (a) activates the RISK pathway via a redox signaling, (b) favors discrete mitochondrial protein S-Nitrosylation, including VDAC and (c) decreases signals of death. Intriguingly, phospho-STAT3 translocation is induced by I-PostC, but not by P-PostC, thus suggesting a redox-independent mechanism in the SAFE pathway.

Cardioprotection against ischemia/reperfusion injury and chromogranin A-derived peptides.

Chromogranin A (CgA) is produced by cells of the sympathoadrenal system and by human ventricular myocardium. In the clinical setting CgA has been mainly used as a marker of neuroendocrine tumors, but in the last decade a plenty of data have been published on the role of CgA and its derived peptides, particularly catestatin and vasostatin, in the regulation of cardiovascular function and diseases, including heart failure and hypertension. CgA-derived peptides, namely catestatin and vasostatin, may exert negative inotropic and lusitropic effects on mammalian hearts. As such CgA and its derived peptides may be regarded as mediators of a complex feedback system able to modulate the exaggerated release of catecholamines. This system may be also interpreted as an attempt for compensatory cardioprotective response against myocardial injury in the pre and postischemic scenarios. In fact, while vasostatin can trigger cardioprotective effects akin ischemic preconditioning (protection is triggered before ischemia), catestatin is a potent cardioprotective agent in the early post-ischemic phase, acting like a postconditioning agent (protection is triggered at the onset of reperfusion). Admittedly, the exact mechanism of cardioprotection of this system is far from being fully understood. Interestingly, both vasostatin and catestatin have shown to be able to activate multiple cardioprotective pathways. In particular, these two CgA-derived peptides may induce nitric oxide dependent pathway, which may play a pivotal role in cardioprotection against ischemia/reperfusion injury. Here, we review the literature about the cardiac effects of catestatin and vasostatin, the mechanisms of myocardial injury and protection and the role of CgA derived peptides in cardioprotection.

Ischemia/reperfusion injury is increased and cardioprotection by a postconditioning protocol is lost as cardiac hypertrophy develops in nandrolone treated rats.

We hypothesized that nandrolone (ND)-abuse induces cardiac hypertrophy, increases myocardial susceptibility to ischemia/reperfusion (I/R) injury, and reduces responsiveness to postconditioning (PostC) cardioprotection. Wistar-rats were ND treated for 2 weeks (short_ND) or 10 weeks (long_ND). Vehicle-treated rats served as controls. Hearts were retrogradely perfused and left ventricular pressure (LVP) was measured before and after 30-min global ischemia. In subgroups of hearts, to induce cardioprotection a PostC protocol (five cycles of 10-s reperfusion and 10-s ischemia) was performed. ß-adrenoreceptors, kinases (Akt and GSK-3ß) and phosphatases (PP2A sub A and PP2A sub B) were examined by Western blot before and after ischemia. After 120-min reperfusion, infarct size was measured. Short_ND slightly increased cardiac/body weight ratio, but did not affect cardiac baseline nor post-ischemic contractile function or infarct size when compared to vehicle hearts. However, PostC limited cardiac dysfunction much more in short_ND hearts than the other groups. Although cardiac/body weight ratio markedly increased after long_ND, baseline LVP was not affected. Yet, post-ischemic contracture and infarct size were exacerbated and PostC was unable to reduce infarct size and ventricular dysfunction. While short_ND increased phosphatases, non-phosphorylated and phosphorylated Akt, long_ND reduced phosphatase-expression and Akt phosphorylation. Both short_ND and long_ND had no effect on the GSK-3ß-phosphorylation but increased the expression of ß(2)-adrenoreceptors. In reperfusion, PostC increased Akt phosphorylation regardless of protective effects, but reduced phosphatase-expression in protected hearts only. In conclusion, short_ND improves post-ischemic myocardial performance in postconditioned hearts. However, long_ND increases myocardial susceptibility to I/R injury and abolishes cardioprotection by PostC. This increased susceptibility might be related to steroid-induced hypertrophy and/or to altered enzyme expression/phosphorylation.

[The mental health service at the pediatric clinic of the University "La Sapienza" in Rome: 1948-2009]. / Il centro di igiene mentale della clinica pediatrica della Università "La Sapienza" di Roma nella seconda meta del secolo scorso.

The article outlines the history of the Mental Health Center operating within the Pediatric Clinic and School of Pediatrics of the University "La Sapienza" in Rome, Italy from 1948 to 2009. The main aim of the Center was to contribute to the understanding of the developmental process in children, to study its promoting factors and, at the same time, to consider the psychological and human implications of health issues. The original idea of the Center was the need to integrate psychological implication in pediatric care. In times of increasing negative technical interferences in the doctor-patient relationship, the Center acted as an open cultural space proposing a medical model concerned with the wholeness of the patient and his psychophysical wellbeing.

Post-ischaemic activation of kinases in the pre-conditioning-like cardioprotective effect of the platelet-activating factor.

AIM: Platelet-activating factor (PAF) triggers cardiac pre-conditioning against ischemia/reperfusion injury. The actual protection of ischaemic pre-conditioning occurs in the reperfusion phase. Therefore, we studied in this phase the kinases involved in PAF-induced pre-conditioning. METHODS: Langendorff-perfused rat hearts underwent 30 min of ischaemia and 2 h of reperfusion (group 1, control). Before ischaemia, group 2 hearts were perfused for 19 min with PAF (2 x 10(-11) M); groups 3-5 hearts were co-infused during the initial 20 min of reperfusion, with the protein kinase C (PKC) inhibitor chelerythrine (5 x 10(-6) M) or the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (5 x 10(-5) M) and atractyloside (2 x 10(-5) M), a mitochondrial permeability transition pore (mPTP) opener respectively. Phosphorylation of PKCepsilon, PKB/Akappat, GSK-3beta and ERK1/2 at the beginning of reperfusion was also checked. Left ventricular pressure and infarct size were determined. RESULTS: PAF pre-treatment reduced infarct size (33 +/- 4% vs. 64 +/- 5% of the area at risk of control hearts) and improved pressure recovery. PAF pre-treatment enhanced the phosphorylation/activation of PKCepsilon, PKB/Akappat and the phosphorylation/inactivation of GSK-3beta at reperfusion. Effects on ERK1/2 phosphorylation were not consistent. Infarct-sparing effect and post-ischaemic functional improvement induced by PAF pre-treatment were abolished by post-ischaemic infusion of either chelerythrine, LY294002 or atractyloside. CONCLUSIONS: The cardioprotective effect exerted by PAF pre-treatment involves activation of PKC and PI3K in post-ischaemic phases and might be mediated by the prevention of mPTP opening in reperfusion via GSK-3beta inactivation.

The platelet activating factor triggers preconditioning-like cardioprotective effect via mitochondrial K-ATP channels and redox-sensible signaling.

Endogenous platelet activating factor (PAF) is involved in heart ischemic preconditioning. PAF can also afford pharmacological preconditioning. We studied whether mitochondrial-ATP-sensitive K(+) (mK(ATP)) channels and reactive oxygen species (ROS) are involved in PAF-induced cardioprotection. In Group 1 control hearts, Langendorff-perfused rat hearts underwent 30 min ischemia and 2 hours of reperfusion. Group 2 hearts, before ischemia, were perfused for 19 min with PAF (2x10(-11) M); Groups 3 and 4 hearts were co-infused with PAF and N-acetyl-L-cysteine or 5-hydroxydecanoate to scavenge ROS or to block mK(ATP) channels, respectively. Left ventricular pressure and infarct size were determined. PAF-pretreatment reduced infarct size (33 +/- 4% vs 64 +/- 4.6 % of the area at risk of control hearts) and improved pressure recovery. Infarct-sparing effect of PAF was abolished by N-acetyl-L-cysteine and 5-hydroxydecanoate. Thus, the cardioprotective effect exerted by PAF-pretreatment involves activation of mK(ATP) channels and redox signaling in pre-ischemic phase.

Synergistic effects against post-ischemic cardiac dysfunction by sub-chronic nandrolone pretreatment and postconditioning: role of beta2-adrenoceptor.

Beta(2)-adrenoreceptor overexpression is beneficial against ischemia/reperfusion (I/R) injury. Whether beta-adrenoreceptors are involved in postconditioning (PostC) is unknown. We investigated whether nandrolone-decanoate (ND)-pretreatment can modulate (1) beta-adrenoreceptor expression and (2) post-ischemic cardiac function in response to I/R and PostC. Finally, we tested whether cardioprotection can be prevented by the inhibition of beta(2)-adrenoreceptors. Isolated rat hearts from ND pretreated (15 mg/kg/day i.m., for 14 days) and untreated-animals underwent 30-min ischemia and 120-min reperfusion. In subgroups, at the end of ischemia a PostC protocol (five cycles of 10-s reperfusion and 10-s ischemia) was applied and/or a beta(2)-adrenoreceptor blocker, ICI-118.551 (10 microM), was infused. Left ventricular pressure (LVP) was measured with an electromanometer, and infarct-size was evaluated using nitro-blue-tetrazolium staining. ND-pretreatment increased beta(2)-adrenoreceptor expression, but did not alter cardiac-weight, LVP and maximum rate of increase of LVP (dP/dt(max)). After I/R, infarct-size was smaller in ND-pretreatment than in untreated-animals. Infarct-size was also reduced by PostC, both in untreated and ND-pretreated animals. Contracture was less marked in ND-pretreated animals. PostC reduced contracture in both ND-pretreated and untreated hearts. Moreover, PostC improved post-ischemic recovery of developed LVP and dP/dt(max) much more in earts of ND-pretreated than untreated-animals. ICI-118.551 abolished ND protection and PostC-protection both in ND-pretreated and untreated hearts. Data show that two-weeks ND-pretreatment induces 1) an overexpression of beta(2)-ARs without cardiac hypertrophy and 2) improves the post-ischemic diastolic and systolic cardiac function. Intriguingly, ND-pretreatment potentiates the improvement of systolic function induced by postconditioning via beta(2)-adrenoreceptor activation.

Prospective audit of short-term concurrent ketamine, opioid and anti-inflammatory ('triple-agent') therapy for episodes of acute on chronic pain.

AIM: This prospective audit was undertaken in order to document the analgesic response and adverse effects of concurrent short-term ('burst') triple-agent analgesic (ketamine, an opioid and an anti-inflammatory agent--either steroidal or non-steroidal) administration, for episodes of acute on chronic pain. The clinical hypothesis in this study is that better pain control may be obtained by simultaneous multiple target receptor blockade. METHOD: The response of 18 patients is reported. The pain and analgesic requirement data for the 24 h before starting triple-agent therapy were compared with the last 24 h on the triple-agent therapy. Patients were then classified as responders or non-responders. RESULTS: According to stringent clinical criteria, 12 out of the 18 patients were classified as responders. The response rate was highest for somatic pain (7/9) and appeared to decrease with duration of prior uncontrolled pain. Only four out of the 18 patients reported adverse effects and all of these were minor. CONCLUSIONS: The results suggest that this 'burst' triple-agent approach is safe and effective in an inpatient palliative care population during episodes of poorly controlled acute on chronic pain, and warrants further investigation to ascertain whether it gives superior results compared to the 'gold-standard' WHO ladder approach.