Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir.

The formation of small hybrid aggregates between excipient and drug molecules is one of the mechanisms that contributes to the solubilization of active principles in pharmaceutical formulations. The characterization of the formation, governing interactions and structure of such entities is not trivial since they are highly flexible and dynamic, quickly exchanging molecules from one to another. In the case of cyclodextrins, this mechanism and the formation of inclusion complexes synergistically cooperate to favour the bioavailability of drugs.

Role of Lithium Doping in P2-NaNiMnO for Sodium-Ion Batteries.

P2-structured NaNiMnO (PNNMO) is a promising Na-ion battery cathode material, but its rapid capacity decay during cycling remains a hurdle. Li doping in layered transition-metal oxide (TMO) cathode materials is known to enhance their electrochemical properties. Nevertheless, the influence of Li at different locations in the structure has not been investigated.

Relationship between live body condition score and carcass fat measures in equine.

Relationships between live body condition score (BCS) and carcass fat depots have not been well established in equine. Our study was designed to quantify the relationship between BCS and fat depot measurements from equine carcasses. Live horses ( = 429) were evaluated immediately prior to immobilization at a commercial equine processor.

Mapping the mind of a fly.

Scientists have created the most detailed map of the fruit fly brain to date, identifying over 25,000 neurons and 20 million synapses.

Sulfobutylether-β-cyclodextrin/5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine nanoassemblies with sustained antimicrobial phototherapeutic action.

Nowadays, novel less-expensive nanoformulations for in situ-controlled and safe delivery of photosensitisers (PSs) against opportunistic pathogens in body-infections areas need to be developed. Antimicrobial photodynamic therapy (aPDT) is a promising approach to treat bacterial infections that are recalcitrant to antibiotics. In this paper, we propose the design and characterization of a novel nanophototherapeutic based on the trade cyclodextrin CAPTISOL® (sulfobutylether-beta-cyclodextrin, SBE-βCD) and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine tetrakis(p-toluenesulfonate) (TMPyP) to fabricate efficient biocompatible systems for aPDT.

Efficacy and Safety of the Glucagon Receptor Antagonist RVT-1502 in Type 2 Diabetes Uncontrolled on Metformin Monotherapy: A 12-Week Dose-Ranging Study.

Objective: Evaluate the safety and efficacy of RVT-1502, a novel oral glucagon receptor antagonist, in subjects with type 2 diabetes inadequately controlled on metformin.

Research Design And Methods: In a phase 2, double-blind, randomized, placebo-controlled study, subjects with type 2 diabetes ( = 166) on a stable dose of metformin were randomized (1:1:1:1) to placebo or RVT-1502 5, 10, or 15 mg once daily for 12 weeks. The primary end point was change from baseline in HbA for each dose of RVT-1502 compared with placebo.

Neuronal morphologies built for reliable physiology in a rhythmic motor circuit.

It is often assumed that highly-branched neuronal structures perform compartmentalized computations. However, previously we showed that the Gastric Mill (GM) neuron in the crustacean stomatogastric ganglion (STG) operates like a single electrotonic compartment, despite having thousands of branch points and total cable length >10 mm (Otopalik et al., 2017a; 2017b).

Verifying, Challenging, and Discovering New Synapses Among Fully EM-Reconstructed Neurons in the Leech Ganglion.

Neural circuits underpin the production of animal behavior, largely based upon the precise pattern of synaptic connectivity among the neurons involved. For large numbers of neurons, determining such "connectomes" by direct physiological means is difficult, as physiological accessibility is ultimately required to verify and characterize the function of synapses. We collected a volume of images spanning an entire ganglion of the juvenile leech nervous system via serial blockface electron microscopy (SBEM).

Both nicotine reward and withdrawal are enhanced in a rodent model of diabetes.

Rationale: It is presently unclear whether diabetic rats experience greater rewarding effects of nicotine and/or negative affective states produced by nicotine withdrawal.

Objective: The present study utilized a rodent model of diabetes to examine the rewarding effects of nicotine and negative affective states and physical signs produced by withdrawal.

Methods: Separate groups of rats received systemic administration of either vehicle or streptozotocin (STZ), which destroys insulin-producing beta cells in the pancreas and elevates glucose levels.

Patterns and distribution of presynaptic and postsynaptic elements within serial electron microscopic reconstructions of neuronal arbors from the medicinal leech Hirudo verbana.

Microscale connectomics involves the large-scale acquisition of high-resolution serial electron micrographs from which neuronal arbors can be reconstructed and synapses can be detected. In addition to connectivity information, these data sets are also rich with structural information, including vesicle types, number of postsynaptic partners at a given presynaptic site, and spatial distribution of synaptic inputs and outputs. This study uses serial block-face scanning electron microscopy (EM) to collect two volumes of serial EM data from ganglia of the medicinal leech.

Pharmacokinetics and pharmacodynamics of single and multiple doses of the glucagon receptor antagonist LGD-6972 in healthy subjects and subjects with type 2 diabetes mellitus.

Aim: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of a novel, oral glucagon receptor antagonist, LGD-6972, in healthy subjects and subjects with type 2 diabetes (T2DM).

Methods: In the single ascending dose study, LGD-6972 (2-480 mg) was administered to healthy subjects (n = 48) and T2DM subjects (n = 8). In the multiple ascending dose study, healthy subjects (n = 12) received a dose of 15 mg LGD-6972 and T2DM subjects (n = 36) received doses of 5, 10 or 15 mg of LGD-6972 daily for 14 days.

Estradiol promotes the rewarding effects of nicotine in female rats.

It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration.

Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats.

Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders.

Extended access to methamphetamine self-administration up-regulates dopamine transporter levels 72 hours after withdrawal in rats.

Previous studies have demonstrated that there are persistent changes in dopamine systems following withdrawal from methamphetamine (METH). This study examined changes in striatal dopamine transporter (DAT), tyrosine hydroxylase (TH) and dopamine receptor 2 (D2) 72 h after withdrawal from METH intravenous self- administration (IVSA). Rats were given limited (1h) or extended (6h) access to METH IVSA (0.

Slow-release of famotidine from tablets consisting of chitosan/sulfobutyl ether β-cyclodextrin composites.

An intermolecular complex formed from a 1:1 weight ratio of chitosan (CS, molecular weight 30 kDa) and sulfobutyl ether β-cyclodextrin (SBE-β-CyD, degree of substitution 7) was less soluble than either of the original components. The release of famotidine from tablets composed of a simple mixture of CS and SBE-β-CyD is slower in media at pH 1.2 than at 6.

Nicotine withdrawal increases stress-associated genes in the nucleus accumbens of female rats in a hormone-dependent manner.

Introduction: Previous work led to our hypothesis that sex differences produced by nicotine withdrawal are modulated by stress and dopamine systems in the nucleus accumbens (NAcc). We investigated our hypothesis by studying intact females to determine whether the mechanisms that promote withdrawal are ovarian-hormone mediated.

Methods: Female rats were ovariectomized (OVX) or received sham surgery (intact) on postnatal day (PND 45-46).

Age-dependent differences in the strength and persistence of psychostimulant-induced conditioned activity in rats: effects of a single environment-cocaine pairing.

The aim of the present study was to determine the strength and persistence of cocaine-induced conditioned activity in young and adult rats. A one-trial protocol has proven useful for studying the ontogeny of psychostimulant-induced behavioral sensitization; therefore, a similar procedure was used to examine conditioned activity. On postnatal day (PD) 19 or PD 80, rats were injected with saline or cocaine in either a novel test chamber or the home cage.

Nicotine exposure beginning in adolescence enhances the acquisition of methamphetamine self-administration, but not methamphetamine-primed reinstatement in male rats.

Background: Nicotine is commonly abused in adolescence and is believed to be a "gateway" to other drugs of abuse [e.g., methamphetamine (METH)].

Phase IIa cross-over study of propylene glycol-free melphalan (LGD-353) and alkeran in multiple myeloma autologous transplantation.

Propylene Glycol-Free melphalan HCL for Injection (PGF-Mel) is a new formulation that incorporates Captisol, a specially modified cyclodextrin, to improve melphalan stability. In this phase IIa, open-label, randomized, cross-over design bioequivalence study, the pharmacokinetics of PGF-Mel were compared with the marketed formulation of melphalan, or Alkeran. Patients received half of the total dose of melphalan in the form of Alkeran and the other half in the form of PGF-Mel in an alternating manner.

Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: implications for teenage smoking.

Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures.

Insulin resistant rats display enhanced rewarding effects of nicotine.

Background: Tobacco use among persons with Type II diabetes exponentially increases negative health consequences and mortality rates. It is especially troubling that diabetic persons who smoke have a greater difficulty with tobacco cessation as compared to non-diabetic smokers. Diabetes is a metabolic syndrome that consists of insulin resistance due to disruptions in insulin signaling.

Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes.

Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water.

Prevalence of low bone mineral density in inpatients with traumatic brain injury receiving neurobehavioural rehabilitation: a postoperative, observational study.

Background: Osteoporosis is characterised by low bone mineral density (BMD) leading to an increased risk of fracture. Patients who have sustained a significant traumatic brain injury may have an increased risk of secondary reduced BMD as a result of immobility and other factors.

Objectives: To describe BMD in a cohort of patients recovering from traumatic brain injury, and to discuss the implications of the findings for physiotherapy practice.