Varenicline increases in vivo striatal dopamine D2/3 receptor binding: an ultra-high-resolution pinhole [123I]IBZM SPECT study in rats

IntroductionEx vivo storage phosphor imaging rat studies reported increased brain dopamine D_2/3 receptor (DRD_2/3) availability following treatment with varenicline, a nicotinergic drug. However, ex vivo studies can only be performed using cross-sectional designs. Small-animal imaging offers the opportunity to perform serial assessments. We evaluated whether high-resolution pinhole single photon emission computed tomography (SPECT) imaging in rats was able to reproduce previous ex vivo findings.MethodsRats were imaged for baseline striatal DRD_2/3 availability using ultra-high-resolution pinhole SPECT (U-SPECT-II) and [¹²³I]IBZM as a radiotracer, and randomized to varenicline (n=7; 2 mg/kg) or saline (n=7). Following 2 weeks of treatment, a second scan was acquired.ResultsSignificantly increased striatal DRD_2/3 availability was found following varenicline treatment compared to saline (time?treatment effect): posttreatment difference in binding potential between groups corrected for initial baseline differences was 2.039 (P=.022), indicating a large effect size (d=1.48).ConclusionsUltra-high-resolution pinhole SPECT can be used to assess varenicline-induced changes in DRD_2/3 availability in small laboratory animals over time. Future small-animal studies should include imaging techniques to enable repeated within-subjects measurements and reduce the amount of animals.     

In vivo [123I]CNS‐1261 binding to D‐serine‐activated and MK801‐blocked NMDA receptors: A storage phosphor imaging study in rats

Disturbances of activity of the glutamatergic neurotransmitter system in the brain are present in many neuropsychiatric disorders. The N‐methyl‐D ‐aspartate (NMDA) receptor is the most abundant receptor of the glutamatergic system. In the neurodegenerative events of Alzheimer's disease, excessive activation of NMDA receptors may contribute to neuronal death. Inhibition of NMDA receptor activation may have neuroprotective effects and (semi)quantitative imaging of the activated system may help in the selection of patients for such inhibition therapies. In this study we evaluated [¹²³I]CNS‐1261 binding in the rat brain. This radiotracer binds in vivo to the MK801 binding site of activated NMDA receptors. To determine the optimal time point for ex vivo assessments after bolus injection [¹²³I]CNS‐1261 binding in rats, we performed a time course biodistribution study using dissection techniques. [¹²³I]CNS‐1261 binding was also studied in the rat brain using autoradiography by means of storage phosphor imaging, with prior facilitation of NMDA receptor activation by injection of the potent coagonist D ‐serine and after blocking of the NMDA receptor binding site by MK801 injection in D ‐serine pretreated rats. Measurements of [¹²³I]CNS‐1261 uptake matched the distribution of similar tracers for the MK801 binding site of the NMDA receptor and revealed an optimal time point of 2 h post injection for the assessment of tracer distribution in the rat brain. The blocking experiments indicated specific binding of [¹²³I]CNS‐1261 to NMDA receptors but also a considerable amount of nonspecific binding. Facilitation of NMDA receptor activation by D ‐serine did not result in an enhancement of binding of the radiotracer in the NMDA receptor‐rich rat hippocampus compared to the untreated group, as measured by autoradiography. In conclusion, our study has shown that [¹²³I]CNS‐1261 binding is influenced by NMDA receptor availability. However, high nonspecific binding limits quantification and small changes in receptor availability are unlikely to be detected. Synapse 63:557–564, 2009. © 2009 Wiley‐Liss, Inc.     

Depression, automatic thoughts, alexithymia, and assertiveness in patients with tension-type headache

OBJECTIVE: The role of psychological factors related to headache has long been a focus of investigation. The aim of this study was to evaluate depression, automatic thoughts, alexithymia, and assertiveness in persons with tension-type headache and to compare the results with those from healthy controls. METHODS: One hundred five subjects with tension-type headache (according to the criteria of the International Headache Society classification) and 70 controls were studied. The Beck Depression Inventory, Automatic Thoughts Scale, Toronto Alexithymia Scale, and Rathus Assertiveness Schedule were administered to both groups. Sociodemographic variables and headache features were evaluated via a semistructured scale. RESULTS: Compared with healthy controls, the subjects with headache had significantly higher scores on measures of depression, automatic thoughts, and alexithymia and lower scores on assertiveness. Subjects with chronic tension-type headache had higher depression and automatic thoughts scores than those with episodic tension-type headache. CONCLUSIONS: These findings suggested that persons with tension-type headache have high depression scores and also may have difficulty with expression of their emotions. Headache frequency appears to influence the likelihood of coexisting depression.     

Increasing availability of benzodiazepines among people who inject drugs in a Canadian setting

ABSTRACT

Background: Benzodiazepine misuse is associated with mortality and is common among people who inject drugs (PWID). This study aimed to examine the temporal trends in the availability of benzodiazepines among PWID in a Canadian setting, and to identify factors associated with more immediate access to benzodiazepines. Methods: Data were derived from 3 prospective cohorts of PWID in Vancouver, Canada, between June 2012 and May 2015. The primary outcome was the perceived availability of benzodiazepines, measured in 3 levels: not available, delayed availability (available in ≥10 minutes), and immediate availability (available in <10 minutes). The authors used multivariable generalized estimating equations to identify factors associated with availability of benzodiazepines. Results: In total, 1641 individuals were included in these analyses. In multivariable analyses, factors associated with immediate benzodiazepine availability included incarceration (adjusted odds ratio [AOR]: 1.42, 95% confidence interval [CI]: 1.06, 1.89) and participation in methadone maintenance therapy (MMT) (AOR: 1.35, 95% CI: 1.14, 1.60). Factors associated with delayed benzodiazepine availability included incarceration (AOR: 1.45, 95% CI: 1.02, 2.07) and participation in MMT (AOR: 1.77, 95% CI: 1.48, 2.12). Benzodiazepine availability increased throughout the study period for both immediate (AOR: 1.14, 95% CI: 1.10, 1.18 per 6-month follow-up period) and delayed (AOR: 1.17, 95% CI: 1.12, 1.22 per 6-month follow-up period) availability. Conclusions: Among our sample of PWID, benzodiazepine availability is increasing and was associated with health and criminal justice system characteristics. Our findings indicate a need to examine prescribing practices and educate both PWID and health care providers about the risks associated with benzodiazepine use.     

A new polyvinylchloride blood bag plasticized with less-leachable phthalate ester analogue, di-n-decyl phthalate, for storage of platelets

To compare changes in platelets stored in the new di-n-decyl phthalate (DnDP)-plasticized polyvinyl chloride (PVC) bag with those in a di-(2-ethylhexyl) phthalate (DEHP)-plasticized PVC bag, single-donor apheresis platelet concentrates (PCs), 133 +/- 11 x 10(7) platelets per ml (n = 7), were stored with 94 +/- 3 ml of plasma in a new 1-liter bag with a surface area of 44 +/- 7.1 cm2 per 10(10) platelets. Oxygen and carbon dioxide gas diffusion properties of PVC-DnDP films were respectively, 1.6 and 2 times those of standard PVC-DEHP films. The amounts of DnDP leaked into the plasma of PCs were low at 0.58 +/- 0.06 mg per bag after 5-day storage, which is about one-eightieth the amount of DEHP leaked. The pH of PCs in PVC-DnDP bags amounted to 6.99 +/- 0.03 after 5-day storage, with glycolysis accelerated somewhat in the new bags. However, the platelet oxygen consumption was no different from that in the PVC-DEHP bags. Platelet aggregation and responses to hypotonic shock were significantly better in the new bags at the end of storage. Shape changes of platelets into spherical forms with dendrites were more frequently observed in PVC-DnDP bags than in PVC-DEHP bags. The study indicated that platelets stored in the new DnDP-plasticized PVC bags have retained aggregation and responses to hypotonic shock more than platelets in the PVC-DEHP bags, but spherical forms and anaerobic metabolism increased in the new bags.     

Warming Effect on Miriplatin–Lipiodol Suspension as a Chemotherapeutic Agent for Transarterial Chemoembolization for Hepatocellular Carcinoma: Preliminary Clinical Experience

Purpose

To retrospectively elucidate the preliminary clinical impact of warmed miriplatin–lipiodol suspension (MPT-LPD) when used as a chemotherapeutic agent for transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).

Materials and Methods

Between June and December 2010, TACE was performed with MPT-LPD at room temperature (RT group), and after January 2011, TACE with MPT-LPD warmed to 40 °C was performed (W group). The intraarterial appearance of MPT-LPD immediately after injection through microcatheters at the second-order branches was compared between the two groups with a 5-point grading system. Local therapeutic effects of HCCs as assessed by follow-up computed tomography (CT) obtained 1–3 months after TACE were compared between the groups with a 4-point grading system (TE1–TE4). After April 2011, angiography-assisted CT was routinely performed at TACE, and HCCs that revealed apparent corona enhancement (CE) were retrospectively selected. The degree of concordance between CE and MPT-LPD accumulation as assessed by CT immediately after TACE was assessed with a 3-point grading scale.

Results

MPT-LPD therapy resulted in a smooth and continuous appearance in the W group (grades 1, 2, 3, 4, and 5 were, respectively, 1, 2, 11, 18, and 4) compared to the RT group (4, 0, 1, 2, and 0). The W group (TE1, TE2, TE3, and TE4 were 1, 9, 11, and 12) revealed better local therapeutic effects than the RT group (6, 3, 9, and 0) (p < 0.05). CE was found in 26 HCC nodules, and concordance between CE and MPT-LPD accumulation was observed in 66 % (grades 1, 2, and 3 were, respectively, 2, 8, and 19).

Conclusion

Warmed MPT-LPD flowed more smoothly within vascular lumen, passed through tumor sinusoid of HCC, and had better local therapeutic effects at short-term observation than MPT-LPD at room temperature.