Revolutionary Impact of Nanodrug Delivery on Neuroscience

Brain research is the most expanding interdisciplinary research that is using the state of the art techniques to overcome limitations in order to conduct more accurate and effective experiments. Drug delivery to the target site in the central nervous system (CNS) is one of the most difficult steps in neuroscience researches and therapies. Taking advantage of the nanoscale structure of neural cells (both neurons and glia); nanodrug delivery (second generation of biotechnological products) has a potential revolutionary impact into the basic understanding, visualization and therapeutic applications of neuroscience. Current review article firstly provides an overview of preparation and characterization, purification and separation, loading and delivering of nanodrugs. Different types of nanoparticle bioproducts and a number of methods for their fabrication and delivery systems including (carbon) nanotubes are explained. In the second part, neuroscience and nervous system drugs are deeply investigated. Different mechanisms in which nanoparticles enhance the uptake and clearance of molecules form cerebrospinal fluid (CSF) are discussed. The focus is on nanodrugs that are being used or have potential to improve neural researches, diagnosis and therapy of neurodegenerative disorders.     

Non-steroidal anti-inflammatory drugs in colorectal surgery: A risk factor for anastomotic complications?

In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significantly higher among patients who were administered non-steroidal anti-inflammatory drugs (NSAIDs) in the perioperative course. A dose-response relationship could also be traced, where longer NSAID use yielded a higher risk of anastomotic breakdown. However, as this study is observational in design, confounding by indication may be present and there is also a risk of residual confounding from unmeasured covariates. Moreover, the question whether different affinity for the cyclooxygenase enzyme is important in different NSAIDs seems to be largely unanswered. The results, conclusions and clinical relevance of the aforementioned study, including the possible effects of different types of NSAIDs, are discussed. While acknowledging that this study represents the best attempt so far in establishing the causal relationship between perioperative NSAID use and anastomotic leakage, the need for further research in this important area is underlined.     

Facts and Fallacies About Measuring Blood Pressure in Rats

Although blood pressure can easily be measured in anesthetized rats by simply connecting a catheter to a pressure transducer, repeated measurements taken over long periods of time in awake rats are much more difficult to make. For chronic experiments two methods are now commonly used: direct recording from chronically-implanted arterial catheters, or indirect measurement with the tail-cuff method. Direct recording of intraarterial pressure can be done continuously and is more accurate, but technically more demanding. On the other hand, although tail-cuff measurements are less accurate, they do not require surgery and can be repeated almost indefinitely. With most tail-cuff methods the rats are preheated to dilate the tail vessels and thereby facilitate pulse detection, but with the new IITC photoelectric sensor indirect measurements of systolic as well as of mean arterial pressure can be made without external preheating. Even with a properly validated tail-cuff method, however, errors can still occur particularly when it is used to quantify modest blood pressure changes like those during development of hypertension, or following administration of vasoactive drugs. To safeguard against such errors, each laboratory should always validate its own tail-cuff method under uniform experimental conditions similar to those existing when the method is actually used. Additionally, all blood pressure differences thereby detected should be verified by direct measurement of intraarterial pressure in the same rats.     

State-of-the-Art Management of Acute Bleeding Peptic Ulcer Disease

The management of patients with non variceal upper gastrointestinal bleeding has evolved, as have its causes and prognosis, over the past 20 years. The addition of high-quality data coupled to the publication of authoritative national and international guidelines have helped define current-day standards of care. This review highlights the relevant clinical evidence and consensus recommendations that will hopefully result in promoting the effective dissemination and knowledge translation of important information in the management of patients afflicted with this common entity.     

Characteristics of analytically confirmed 3-MMC-related intoxications from the Swedish STRIDA project

Abstract

Background. 3-Methylmethcathinone (3-MMC) is a synthetic cathinone stimulant structurally related to the new psychoactive substance (NPS) mephedrone (4-methylmethcathinone, 4-MMC). We describe a case series of analytically confirmed intoxications involving 3-MMC presented to emergency departments in Sweden and included in the STRIDA project. Study design. Observational case series of consecutive patients with self-reported or suspected use of NPS presenting to hospitals in Sweden between August 2012 and March 2014. Methods. NPS analysis was performed by a liquid chromatography–mass spectrometry (MS)/MS method that is updated with new substances as they appear. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. Results. 3-MMC was detected in 50 (6.4%) of the 786 cases included in the STRIDA project during the 20-month study period, with the peak occurring in August 2013. The age range of patients testing positive for 3-MMC was 17–49 years (median 24) and 76% of them were men. The 3-MMC concentration in serum ranged between 0.002 and 1.49 μg/mL (median, 0.091) and between 0.007 and 290 μg/mL (median, 3.05) in urine. Co-exposure to other NPS and/or traditional drugs was very common, and 3-MMC mono-intoxication was found in only 4 (8%) cases. The most frequent clinical features were tachycardia (48% of cases) and agitation (42%). Other features included a reduced level of consciousness (32%), dilated pupils (24%), hallucinations (20%), diaphoresis (12%), seizures (8%), and hyperthermia (6%). Most patients (60%) needed hospital care for only 1 day but in 8% for 3 days or longer. Conclusion. The majority of patients with analytically confirmed 3-MMC exposure had sympathomimetic features similar to those associated with mephedrone intoxication. However, the high incidence of co-exposure to other drugs makes the clinical interpretation difficult. Nevertheless, 3-MMC was associated with a high admittance rate to intensive care (30%), and detected in two cases with a fatal outcome, suggesting that 3-MMC is a harmful drug.     

Intentional ingestion of cyanoacrylate

Abstract

Background. Diphenidine (1-(1,2-diphenylethyl)piperidine) and its 2-methoxylated derivative methoxphenidine (MXP, 2-MeO-diphenidine) are substances with dissociative effects that were recently introduced for “recreational” purpose through the online-based sale of new psychoactive substances (NPS). A number of analytically confirmed non-fatal intoxications associated with diphenidine or MXP have occurred in Sweden and were included in the STRIDA project. Study design. Observational case series of consecutive patients with admitted or suspected intake of NPS and requiring intensive treatment in an emergency room and hospitalization in Sweden. Patients and methods. Blood and urine samples were collected from intoxicated patients presenting at emergency departments all over the country. NPS analysis was performed by multi-component liquid chromatography–mass spectrometry methods. Data on clinical features were collected during telephone consultations with the Poisons Information Centre and retrieved from medical records. Information was also obtained from online drug discussion forums. Case series. Over a 12-month period from January to December 2014, 750 cases of suspected NPS intoxication originating from emergency departments were enrolled in the STRIDA project of which 14 (1.9%) tested positive for diphenidine and 3 (0.4%) tested positive for MXP. Co-exposure to several other NPS (e.g., 5-/6-(2-aminopropyl)benzofuran, 2-4-bromomethcathinone, butylone, 3,4-dichloromethylphenidate, 5-methoxy-N-isopropyltryptamine, methiopropamine, and α-pyrrolidinopentiothiophenone), also including other dissociative substances (3-/4-methoxyphencyclidine), and classical drugs of abuse (e.g., cannabis and ethanol) was documented in 87% of these cases. The 17 patients were aged 20–48 (median: 32) years, and 13 (76%) were men. They commonly presented with hypertension (76%), tachycardia (47%), anxiety (65%), and altered mental status (65%) including confusion, disorientation, dissociation, and/or hallucinations. Eight patients (47%) displayed severe intoxication (Poisoning Severity Score 3). The diphenidine- or MXP-positive patients required hospitalization for 1–3 (median: 2) days. In addition to standard supportive therapy, half of the cases were treated with benzodiazepines and/or propofol. Conclusion. The adverse effects noted in analytically confirmed cases of NPS intoxication involving diphenidine or MXP were similar to those reported for other dissociative substances such as ketamine and methoxetamine. However, the high proportion of polysubstance use might have played a role in the intoxication and clinical features in some cases.     

Motivational Interviewing, 2nd ednWilliam Miller and Stephen RollnickThe Guilford Press. ISBN: 1‐572‐30563‐0, 2002, 428 pp with index, £26.95 (hbk)

More people with intellectual disability are living independent lives. They can and do experiment with substances that the wider community try, such as alcohol and drugs (both legal and illicit). Unfortunately for some, they develop problems related to their use of these substances. Face‐to‐face, semi‐structured interviews were conducted with 13 professionals who work in Intellectual Disability Services and Alcohol &; Drug Services to discover their experiences of caring for people with intellectual disabilities who hazardously use substances. Although small numbers of people presented to these services, many more people with intellectual disabilities used Intellectual Disability Services for support, rather than their local Alcohol &; Drug Services. While the numbers may be relatively small, the challenges this client group pose are very perturbing in relation to their physical, emotional and social health. The professionals reported a lack of education in working with this doubly disadvantaged population. Moreover, policies were absent to guide staff to work collaboratively with this often‐ignored population. These findings are discussed in light of the innovative practices that are occurring in other parts of the UK regarding the recognition, assessment treatment and long‐term management of this population. Intellectual Disability Services and Alcohol &; Drug Services need to work more closely together if the needs of this population are to be effectively met.