ABHD6 inhibition rescues a sex-dependent deficit in motor coordination in the HdhQ200/200 mouse model of Huntington’s disease

Huntington’s Disease is associated with motor behavior deficits that current therapeutics do not alleviate. This pilot study tested if pharmacological inhibition of a/b-hydrolase domain containing 6 (ABHD6), a multifunctional enzyme expressed in the striatum, rescues behavioral deficits in HdhQ200/200 mice. Previous work has shown that this model exhibits a reduction in spontaneous locomotion and motor coordination at 8 and 10 months of age, with a more severe phenotype in female mice. Semi-quantitative immunohistochemistry analysis indicated no change in striatal ABHD6 expression at 8 months of age, but a 40% reduction by 10 months in female HdhQ200/200 mice compared to female wild-type (WT) littermates. At 8 months of age, acute ABHD6 inhibition selectively rescued motor coordination deficits in female HdhQ200/200 mice without affecting WT performance. ABHD6 inhibition did not impact spontaneous locomotion, grip strength or overall weight in either group, showing that effects were specific to motor coordination. At 10 months of age, semi-chronic ABHD6 inhibition by osmotic pump delivery also rescued motor coordination deficits in female HdhQ200/200 mice without affecting female WT littermates. Our preliminary study suggests that ABHD6 inhibition selectively improves motor performance in female HdhQ200/200 mice.

Evaluation of Technical Condition of Round Gear Hydraulic Pumps of Tractor Mounted Hydraulic Systems

Introduction. In the technical service enterprises, the reliable estimation of a technical condition of hydraulic gear pumps of tractor mounted hydraulic systems is a priority in introducing new repair processes. The absence of data of manufacturing plants on limiting wear of working surfaces of hydraulic pump details, when the decision on repair is taken, leads to the necessity of carrying out additional researches. In this regard, the purpose of work is to find the limit wear values for working surfaces of details of round gear hydraulic pumps. Materials and Methods. The laboratory tests of used round gear hydraulic pumps were carried out according to the method developed in the GOSNITI on the hydraulic bench of the KI-28097M-GOSNITI. The controlled parameter during tests is the pump delivery rate. Results. The results of laboratory bench and micrometer studies of used round gear hydraulic pumps are presented in the work. The mathematical model of pump delivery rate dependence on statistically significant independent factors is obtained. The limit values for wear of working surfaces of round gear hydraulic pump details are determined by the steepest ascent method on the received mathematical model. Discussion and Conclusion. According to the results of the input bench control of the used round gear pumps, 81% of the tested units were operated in the over-extreme limit state. The limit values for wear of working surfaces of round gear hydraulic pump details obtained by the steepest ascent method make it possible to make a conclusion about the necessity of their restoration in repairing at technical service enterprises.

Evaluating infusate parameters for direct drug delivery to the brainstem: a comparative study of convection-enhanced delivery versus osmotic pump delivery

OBJECTIVEConvection-enhanced delivery (CED) and osmotic pump delivery both have been promoted as promising techniques to deliver drugs to pediatric diffuse intrinsic pontine gliomas (DIPGs). Correspondingly, the aim of this study was to understand how infusate molecular weight (MW), duration of delivery, and mechanism of delivery (CED or osmotic pump) affect volume of distribution (Vd) in the brainstem, to better inform drug selection and delivery in future DIPG investigations.METHODSA series of in vivo experiments were conducted using rat models. CED and osmotic pump delivery systems were surgically implanted in the brainstem, and different MW fluorescent dextran beads were infused either once (acute) or daily for 5 days (chronic) in a volume infused (Vi). Brainstems were harvested after the last infusion, and Vd was quantified using serial sectioning and fluorescence imaging.RESULTSFluorescence imaging showed infusate uptake within the brainstem for both systems without complication. A significant inverse relationship was observed between infusate MW and Vd in all settings, which was distinctly exponential in nature in the setting of acute delivery across the 570-Da to 150-kDa range. Chronic duration and CED technique resulted in significantly greater Vd compared to acute duration or osmotic pump delivery, respectively. When accounting for Vi, acute infusion yielded significantly greater Vd/Vi than chronic infusion. The distribution in CED versus osmotic pump delivery was significantly affected by infusate MW at higher weights.CONCLUSIONSHere the authors demonstrate that infusate MW, duration of infusion, and infusion mechanism all impact the Vd of an infused agent and should be considered when selecting drugs and infusion parameters for novel investigations to treat DIPGs.

Insulin Pumping Patches: Emerging Insulin Delivery Systems

In this special section of JDST, patch-pump delivery systems (“patch pumps”) are discussed. Patch pumps are novel insulin delivery systems that have emerged on the market; offering flexible insulin delivery options. These systems offer several advantages over conventional insulin pump delivery systems and are gaining popularity. Patch pumps are free of tubing, small, and lightweight. In this special section, the authors discuss both the simple and complex patch pumps currently available on the US market as well as those that are currently under development. Current technologies used to operate these pumps are discussed in detail, and potential promising technologies are presented. Available data on patient preferences, clinical trial data, and the future of patch pumps are discussed.

Novel Bluetooth-Enabled Tubeless Insulin Pump: Innovating Pump Therapy for Patients in the Digital Age

The Omnipod DASH™ Insulin Management System (Insulet Corp, Billerica, MA) is a discreet, tubeless, wearable insulin pump that holds up to 200 units of U-100 insulin and delivers therapy through customizable basal rates and bolus amounts. This recently FDA-cleared system consists of the insulin pump (“Pod”), which is worn on body and delivers insulin, and the Personal Diabetes Manager (PDM), which is a handheld device used to wirelessly control and monitor the Pod functionality. The PDM can also be paired with the CONTOUR® NEXT ONE blood glucose (BG) meter (Ascensia Diabetes Care, Basel, Switzerland) to wirelessly receive BG readings. This review provides a detailed description of the Pod and PDM. Key features of the Pod are described, including the novel pump delivery mechanism, waterproof (IP28) housing design, and automated cannula insertion. The technology introduced in the new system, such as touchscreen PDM interface, Bluetooth® wireless technology, and wireless internet connectivity, is also presented. Last, Omnipod® Insulin Management System clinical data are reviewed, including early feasibility results for the Omnipod Horizon™ Automated Glucose Control hybrid closed-loop system.