Reno-protective effects of Phosphodiesterase 5 inhibitors

Clinical and Experimental Nephrology - The kidneys are vital organs that play an important role in removing waste materials from the blood, electrolyte balance, blood pressure regulation, and red...     

Arginine and Disordered Amyloid-β Peptide Structures: Molecular Level Insights into the Toxicity in Alzheimer’s Disease

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The Structures of the E22Δ Mutant-Type Amyloid-β Alloforms and the Impact of E22Δ Mutation on the Structures of the Wild-Type Amyloid-β Alloforms

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Probing and Trapping a Sensitive Conformation: Amyloid-β Fibrils, Oligomers, and Dimers

Alzheimer's disease (AD) is a devastating neurodegenerative disease with pathological misfolding of amyloid-β protein (Aβ). The recent interest in Aβ misfolding intermediates necessitates development of novel detection methods and ability to trap these intermediates. We speculated that two regions of Aβ may allow for detection of specific Aβ species: the N-terminal and 22-35, both likely important in oligomer interaction and formation. We determined via epitomics, proteomic assays, and electron microscopy that the Aβ42 species (wild type, ΔE22, and MetOx) predominantly formed fibrils, oligomers, or dimers, respectively. The 2H4 antibody to the N-terminal of Aβ, in the presence of 2% SDS, primarily detected fibrils, and an antibody to the 22-35 region detected low molecular weight Aβ species. Simulated molecular modeling provided insight into these SDS-induced structural changes. We next determined if these methods could be used to screen anti-Aβ drugs as well as identify compounds that trap Aβ in various conformations. Immunoblot assays determined that taurine, homotaurine (Tramiprosate), myoinositol, methylene blue, and curcumin did not prevent Aβ aggregation. However, calmidazolium chloride trapped Aβ at oligomers, and berberine reduced oligomer formation. Finally, pretreatment of AD brain tissues with SDS enhanced 2H4 antibody immunostaining of fibrillar Aβ. Thus we identified and characterized Aβs that adopt specific predominant conformations (modified Aβ or via interactions with compounds), developed a novel assay for aggregated Aβ, and applied it to drug screening and immunohistochemistry. In summary, our novel approach facilitates drug screening, increases the probability of success of antibody therapeutics, and improves antibody-based detection and identification of different conformations of Aβ.     

Hospital acquired infections (HAI) in the elderly: comparison with the younger patients

The aim of this retrospective study is to determine the frequency, type, microbiological characteristics and outcome of HAIs in the elderly (age ≥ 65) and to compare the data with younger patients in a Turkish Training and Research Hospital. From January 2008 to December 2009, the infection control team analyzed HAIs among 60,585 hospitalized patients (20,109 aged ≥ 65 and 40,747 aged between 18 and 64 years) with a total number of 419,017 patient days. A total of 825 HAIs episodes were detected in 607 patients, of which 395 episodes were in 301 elderly patients. The incidence of HAIs per 1000 patient days was 2.49 in the elderly and 1.64 in the younger patients’ group (p < 0.001). The most common site of infection in the elderly patients was the urinary tract, whereas in non-elderly group this was the lower respiratory tract. The incidence density of urinary tract infections, respiratory tract infections, surgical site, skin and soft tissue infections, primary bacteremia, and prosthesis infections were significantly higher in the elderly group (p < 0.05). Gram-negative species were the most frequently isolated agents in both groups. There were no significant differences between the groups in the frequency of isolated pathogens or antibiotic susceptibility patterns. Overall, the fatality rate was found 16.8%. The elderly patients were more likely to have crude mortality rates (22% vs. 12%; p < 0.01). The death was most often related to pneumonia, primary bacteremia or intravascular catheter infections in both groups.     

Cilostazol and diltiazem attenuate cyclosporine-induced nephrotoxicity in rats

Aim

Cyclosporine (CsA), an important agent used in organ transplantation to prevent rejection, displays nephrotoxicity as the most important side effect limiting usage. In this study, we sought to evaluate the effects of cilostazol and diltiazem to counter the nephrotoxicity induced by the calcineurin inhibitor CsA.

Materials and methods

Animals were randomly divided into seven groups, each consisting of eight animals: sham, controls, cilostazol, diltiazem, CsA, CsA plus diltiazem, and CsA plus cilostazol treatment. At the end of a 60-minute ischemic period, we administered the drugs after reperfusion for 7 days thereafter. CsA (10 mg/kg/d) was intraperitoneally for 7 days; cilostazol (10 mg/kg/d) orally by catheter for 7 days; diltiazem (5 mg/kg/d) intraperitoneally for 7 days. At the end of the 7-day treatment period, blood and tissue samples were harvested for biochemical, and serological evaluation.

Results

Ischemia-reperfusion injury significantly increased malondialdehyde (MDA) levels as well as decreased catalase (CAT) activities and superoxide dysmutase (SOD) content. The lowest MDA mean level was observed in the diltiazem and, the highest in the control group. The lowest CAT mean levels were noted in the CsA and diltiazem groups with highest CAT content was in the CsA and cilostazol groups. The lowest SOD mean level occurred in the sham group; the highest, in the CsA group.

Conclusion

Cilostazol and especially diltiazem were effective to mitigate renal ischemia-reperfusion injury.     

Effects of dexmedetomidine on the duration of anaesthesia and wakefulness in bupivacaine epidural block

BACKGROUND: The purpose of this study was to examine the effects of intravenous dexmedetomidine on the duration of bupivacaine-induced epidural anaesthesia and level of wakefulness and the respective side-effects. METHODS: Sixty ASA I-II patients were included in the study. Consecutive patients were allocated to groups according to the last digit (odd/even) of their admission numbers. All patients had epidural anaesthesia with bupivacaine 0.5% performed by the same experienced anaesthesiologist. In the first group, the patients were administered intravenous dexmedetomidine infusion just after the epidural block and continued during the operation, while those in the second group were administered physiologic saline infusion at the same amount and duration. RESULTS: The recovery time of sensory block was significantly longer in the first group. The bispectral index values were lower in the first group than in the second. Also, heart rate was significantly lower in Group I than in Group II. Regarding side-effects, shivering was significantly less frequent in the first group, whereas there was a significant increase in the requirement of atropine in the first group as dexmedetomidine caused bradycardia. CONCLUSION: Intravenous administration of dexmedetomidine prolonged the duration of epidural anaesthesia, provided sedation and had few side-effects.