Nanotechnologies for Alzheimer's disease: diagnosis, therapy, and safety issues

Alzheimer's disease (AD) represents the most common form of dementia worldwide, affecting more than 35 million people. Advances in nanotechnology are beginning to exert a significant impact in neurology. These approaches, which are often based on the design and engineering of a plethora of nanoparticulate entities with high specificity for brain capillary endothelial cells, are currently being applied to early AD diagnosis and treatment. In addition, nanoparticles (NPs) with high affinity for the circulating amyloid-β (Aβ) forms may induce “sink effect” and improve the AD condition. There are also developments in relation to in vitro diagnostics for AD, including ultrasensitive NP-based bio-barcodes, immunosensors, as well as scanning tunneling microscopy procedures capable of detecting Aβ₁₋₄₀ and Aβ₁₋₄₂. However, there are concerns regarding the initiation of possible NP-mediated adverse events in AD, thus demanding the use of precisely assembled nanoconstructs from biocompatible materials. Key advances and safety issues are reviewed and discussed.

From the Clinical Editor

This excellent review summarizes the impact of nanotechnology on the diagnosis and treatment of Alzheimer’s disease, ranging from circulating amyloid “sinks” to NP-based bio-barcodes and many other recent advances, without neglecting potential pitfalls, side effects and safety issues. A must read for anyone interested in the evolving interface of clinical neurosciences and nanotechnology.     

Protective effect of hawthorn extract against genotoxicity induced by methyl methanesulfonate in human lymphocytes

The preventive effect of hawthorn (Crataegus microphylla) fruit extract against genotoxicity induced by methyl methanesulfonate (MMS) has been investigated in human cultured blood lymphocytes. Peripheral blood samples were collected from human volunteers at 0 (10 minutes before), and at 1 and 2 hours after a single oral ingestion of 1 g hawthorn powder extract. At each time point, the whole blood was treated in vitro with MMS (200 μmol) at 24 hours after cell culture, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cells. The lymphocytes treated with hawthorn and MMS to exhibit a significant decreasing in the incidence of micronucleated binucleated cells, as compared with similarly MMS-treated lymphocytes from blood samples collected at 0 hour. The maximum protection and decreasing in frequency of micronuclei (36%) was observed at 1 hour after ingestion of hawthorn extract. The high performance liquid chromatography (HPLC) analysis showed that hawthorn contained chlorogenic acid, epicatechin and hyperoside. It is obvious that hawthorn, particularly flavonoids constituents with antioxidative activity, reduced the oxidative stress and genotoxicity induced by toxic compounds. This set of data may have an important application for the protection of human lymphocyte from the genetic damage and side effects induced by chemicals hazardous in people.     

A comparative study of three treatment methods of direct pulp capping in canine teeth of cats: a histologic evaluation

Direct pulp capping (DPC) is coverage of exposed pulp by a biocompatible material after traumatic or carious exposure. The purpose of this procedure is to seal this spot against bacterial leakage, stimulate dentinal barrier formation, and maintain the vitality of the pulp. Several factors contribute to the consequence of this treatment, such as the kind of material used and the procedural technique. The aim of this study was to evaluate histologically the outcome of DPC using three methods. Thirty-six canine teeth of nine cats were selected for this experiment. After the cats had been anesthetized, the teeth were exposed under sterile condition. The teeth were randomly divided into three groups. In group I, the exposed pulp was covered with mineral trioxide aggregate (MTA) alone. In group II, the pulp, after being treated with erbium:yttrium-aluminum-garnet (Er:YAG) laser (energy = 200 mJ, pulse duration = 700 micros, repetition rate = 3 Hz, exposure time = 15 s, no air, no water, beam diameter = 0.6 mm), was covered with MTA. In group III, the pulp was treated with laser and covered with calcium hydroxide [Ca(OH)(2)]. All cavities were filled with amalgam after DPC. After 4 months, the animals were sacrificed and block sections were prepared. The specimens were histologically evaluated. The data were analyzed by Mann-Whitney and chi-square tests. Dentinal barrier had formed in all groups. The laser + MTA group showed little superiority to the other groups in dentinal barrier formation, type and intensity of inflammatory responses, and soft tissue changes, especially necrosis, but these differences were not statistically significant (P > 0.05). We concluded that laser + MTA produced better healing. According to the conditions in this study, Er:YAG laser could be used in direct pulp capping treatment in combination with both common materials.     

Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats

Aim of the study

Olive (Olea europaea) leaves are used as anti-rheumatic, anti-inflammatory, antinociceptive, antipyretic, vasodilatory, hypotensive, antidiuretic and hypoglycemic agents in traditional medicine. Recently, it has been shown that olive leaf extract (OLE) has calcium channel blocker property; however, its influences on nociceptive threshold and morphine effects have not yet been clarified.

Materials and methods

All experiments were carried out on male Wistar rats. The tail-flick, hot-plate and formalin tests were used to assess the effect of OLE on nociceptive threshold. To determine the effect of OLE on analgesic and hyperalgesic effects of morphine, OLE (6, 12 and 25 mg/kg i.p.) that had no significant nociceptive effect, was injected concomitant with morphine (5 mg/kg and 1 μg/kg i.p., respectively). The tail-flick test was used to assess the effect of OLE on anti- and pro-nociceptive effects of morphine.

Results

The data showed that OLE (50-200 mg/kg i.p.) could produce dose-dependent analgesic effect on tail-flick and hot-plate tests. Administration of 200 mg/kg OLE (i.p.) caused significant decrease in pain responses in the first and the second phases of formalin test. In addition, OLE could potentiate the antinociceptive effect of 5 mg/kg morphine and block low-dose morphine-induced hyperalgesia.

Conclusion

Our results indicate that olive leaf extract has analgesic property in several models of pain and useful influence on morphine analgesia in rats. Therefore, it can be used for the treatment and/or management of painful conditions.     

Bilateral renal lymphangiomatosis: sonographic findings

Renal lymphangiomatosis is an exceedingly rare disorder characterized by developmental malformation of the lymphatic system surrounding the kidneys. We report a case of bilateral renal lymphangiomatosis in a 21-year-old man who underwent abdominal sonographic examination that revealed numerous cystic areas of various sizes around both kidneys with extension along the renal hilum. Subsequent abdominal CT examination demonstrated bilateral, multilocular, fluid-filled cystic masses with thin walls in the perirenal and peripelvic region. MRI of the patient revealed bilaterally enlarged kidneys with multiple hyperintense lesions in both perirenal spaces and the peripelvic area on T2-weighted images. These cystic spaces appeared hypointense on T1-weighted images with no enhancement in postcontrast images. The diagnosis of renal lymphangiomatosis was made based on typical imaging findings.     

Crimean-Congo hemorrhagic fever among health care workers in Iran: a seroprevalence study in two endemic regions

Crimean-Congo hemorrhagic fever (CCHF) has repeatedly caused nosocomial outbreaks among hospital staff. In the summer of 2003, we studied the seroprevalence of anti-CCHF IgG among health care workers who had come in contact with Crimean-Congo hemorrhagic fever patients from three referral hospitals in endemic regions of Iran. A total of 223 eligible staff were examined. Whereas 5 of 129 (3.87%) exposed health care workers tested positive, none of the 94 in the unexposed group did (P=0.075). Seropositivity was more frequent among those whose intact skin had come in contact with nonsanguineous body fluids (9.52%) and those who had had percutaneous contacts (7.14%). Health care workers exposed to Crimean-Congo hemorrhagic fever patients, those who live in Systan-Baluchestan province, and older health care workers were more prone to seropositivity. Where introduction of high-risk modes of contact cannot be confined, we propose that health care workers take all the protective measures when handling Crimean-Congo hemorrhagic fever patients, particularly their blood and other body fluids.     

Pharmacological prevention of the deleterious effects of cardiopulmonary bypass

Indomethacin is a known immune modulator that inhibits cyclooxygenase. Studies indicate that ketoconazole, a selective lipoxygenase and thromboxane A(2) synthetase inhibitor, can prevent activation of the inflammatory cascade by inhibition of proinflammatory mediators. This study was designed to determine if ketoconazole or indomethacin could reduce the adverse effects of extracorporeal circulation. As a double-blind prospective study, 76 patients were randomized into 3 groups according to preoperative medication: indomethacin, ketoconazole, and placebo groups, with 25, 26, and 25 patients, respectively. Four types of parameters were evaluated preoperatively and up to 24 hr after cardiac surgery in all patients: inflammatory (complement C3 and C4, C-reactive protein, immunoglobulins); hematologic; coagulation; and physiologic (blood loss, fluid and blood components received, weight gain, and duration of ventilation). Statistical analyses showed similar patient profiles in each group. Complement C4 decreased in all groups postoperatively, but significantly less in the indomethacin group ( p < 0.01). Ketoconazole reduced postoperative bleeding ( p < 0.0001) as well as the incidence of re-operation for bleeding ( p = 0.05). It was concluded that indomethacin decreases complement (specifically C4) consumption during cardiopulmonary bypass, and ketoconazole may reduce postoperative bleeding by limiting coagulation abnormalities in cardiac surgery patients.