The Role of Atypical Cannabinoid Ligands O-1602 and O-1918 on Skeletal Muscle Homeostasis with a Focus on Obesity.

O-1602 and O-1918 are atypical cannabinoid ligands for GPR55 and GPR18, which may be novel pharmaceuticals for the treatment of obesity by targeting energy homeostasis regulation in skeletal muscle. This study aimed to determine the effect of O-1602 or O-1918 on markers of oxidative capacity and fatty acid metabolism in the skeletal muscle. Diet-induced obese (DIO) male Sprague Dawley rats were administered a daily intraperitoneal injection of O-1602, O-1918 or vehicle for 6 weeks.

Uptake of leptin and albumin via separate pathways in proximal tubule cells.

The adipokine leptin and oncotic protein albumin are endocytosed in the proximal tubule via the scavenger receptor megalin. Leptin reduces megalin expression and activates cell signalling pathways that upregulate fibrotic protein expression. The aim of this study was to investigate if leptin uptake in proximal tubule cells was via the albumin-megalin endocytic complex.

Chronic administration of AM251 improves albuminuria and renal tubular structure in obese rats.

Modulation of the endocannabinoid system as an anti-obesity therapeutic is well established; however, the direct effects of cannabinoid receptor 1 (CB1) antagonism on renal function and structure in a model of diet-induced obesity (DIO) are unknown. The aim of this study was to characterise the renal effects of the CB1 antagonist AM251 in a model of DIO. Male Sprague-Dawley rats were fed a low- or high-fat diet (HFD: 40% digestible energy from lipids) for 10 weeks to elicit DIO (n=9).

Acute leptin exposure reduces megalin expression and upregulates TGFβ1 in cultured renal proximal tubule cells.

Increased leptin concentrations observed in obesity can lead to proteinuria, suggesting that leptin may play a role in obesity-related kidney disease. Obesity reduces activation of AMP-activated protein kinase (AMPK) and increases transforming growth factor-β1 (TGF-β1) expression in the kidney, leading to albuminuria. Thus we investigated if elevated leptin altered AMPK and TGF-β1 signaling in proximal tubule cells (PTCs).

Short term exposure to elevated levels of leptin reduces proximal tubule cell metabolic activity.

Leptin plays a pathophysiological role in the kidney, however, its acute effects on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in vitro, Western blot analysis identified that exposure to leptin increases the phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42 and the mammalian target of rapamycin (mTOR). Importantly leptin (0.

Co-ingestion of carbohydrate and whey protein isolates enhance PGC-1α mRNA expression: a randomised, single blind, cross over study.

Background: Whey protein isolates (WPI) supplementation is known to improve resistance training adaptations. However, limited information is available on the effects of WPI plus carbohydrate (CHO) supplementation on endurance training adaptations.

Method: Six endurance trained male cyclists and triathletes (age 29 ± 4 years, weight 74 ± 2 kg, VO2 max 63 ± 3 ml oxygen.

Varicella-zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line.

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects.

Role for cannabinoid receptors in human proximal tubular hypertrophy.

Endogenous endocannabinoids bind to cannabinoid receptors; namely CB1, CB2, TRPV1 and GPR55, to activate intracellular pathways that control many cellular functions. Elevated levels of endocannabinoids have been identified in diseases such as obesity and diabetes, with the onset of diabetic nephropathy associated with proximal tubule hypertrophy. Recent research has identified a role for CB1 in apoptosis in human proximal tubular (HK2) cells, however the role of the other receptors has not been investigated.

Assessment of transcriptomal analysis of Varicella-Zoster-virus gene expression in patients with and without post-herpetic neuralgia.

Varicella-Zoster virus (VZV) is a human herpes virus that reactivates from a latent state in human trigeminal and dorsal root ganglia to cause herpes zoster (shingles) which is a painful vesicular dermatomal skin eruption. The major complication of herpes zoster is post-herpetic neuralgia (PHN) which is a serious condition occurring especially in individuals over 50 years. PHN is extremely painful, may be permanent, and is frequently very refractory to all treatment.

Genome-wide reduction in transcriptomal profiles of varicella-zoster virus vaccine strains compared with parental Oka strain using long oligonucleotide microarrays.

Varicella-Zoster virus (VZV) causes varicella as a primary infection following which it becomes latent in human ganglia and then reactivates to cause herpes zoster. VZV vaccines are used to prevent primary infection with varicella, and also to reduce the incidence of viral reactivation causing herpes zoster and post-herpetic neuralgia. To gain further insights into the molecular basis of their attenuated virulence, we used long oligonucleotide microarrays to determine the lytic transcriptomal profiles of two vaccine VZV strains (Merck and GSK) compared with the Oka parental (P-Oka) strain.

The pattern of viral persistence in monkeys intra-tracheally infected with Simian varicella virus.

In situ PCR (ISPCR) and in situ hybridisation (ISH) was performed on 32 tissues from 10 monkeys, intra-tracheally (IT) infected with simian varicella virus (SVV) and 5 tissues from 3 uninfected control animals. The results showed persistence of SVV DNA up to 2 years post-infection (pi) and the localisation of SVV to be confined to neurons except at time points 9 and 10 months pi where SVV positive satellite cells were also detected. There was no evidence for transcription of SVV ORFs 63 and 21 in the ganglia of the one IT infected and 2 naturally infected monkeys investigated using RNA ISH.

Varicella-Zoster virus gene expression at variable periods following death in a rat model of ganglionic infection.

We used a rat model of Varicella-Zoster virus (VZV) ganglionic infection, which mirrors some of the features of VZV latency in humans, to determine the temporal pattern of expression of a VZV immediate-early gene (63) and a VZV late gene (40) at 0, 24 and 48 h after death of the animal. The immediate-early VZV gene 63 is known to be abundantly expressed during human ganglionic latency, while the late VZV gene 40 is not expressed during human latency. Using both RNA in situ hybridisation (ISH) and nested RT-PCR, it was found that at all time points in both thoracic and lumbar ganglia, the number of ganglia positive for VZV gene 63 was higher than for gene 40.

Transcriptomal analysis of varicella-zoster virus infection using long oligonucleotide-based microarrays.

Varicella-zoster virus (VZV) is a human herpes virus that causes varicella as a primary infection and herpes zoster following reactivation of the virus from a latent state in trigeminal and spinal ganglia. In order to study the global pattern of VZV gene transcription, VZV microarrays using 75-base oligomers to 71 VZV open reading frames (ORFs) were designed and validated. The long-oligonucleotide approach maximizes the stringency of detection and polarity of gene expression.

Translation of varicella-zoster virus genes during human ganglionic latency.

Immunohistochemical analysis of fixed tissue sections of human trigeminal ganglia (TG) and dorsal root ganglia (DRG) revealed the neuronal expression of proteins encoded by Varicella-zoster virus (VZV) genes 21, 29, 62 and 63. These proteins were detected mainly in the neuronal cytoplasm, are likely to be present in low abundance during VZV latency, and mirror the profile of VZV gene transcription.

Neuronal localization of simian varicella virus DNA in ganglia of naturally infected African green monkeys.

In situ hybridization analysis of monkey ganglia 2 months after natural infection with simian varicella virus (SVV) revealed SVV DNA only in neurons. These findings parallel the detection of varicella zoster virus in neurons of latently infected human ganglia. Natural exposure to SVV provides a model system to study varicella latency.

Varicella-Zoster virus proteins encoded by open reading frames 14 and 67 are both dispensable for the establishment of latency in a rat model.

A rat model of Varicella-Zoster virus (VZV) provides a system in which to investigate the molecular determinants of viral latency in dorsal root ganglia (DRG). In this study, we determined whether the VZV glycoproteins gC and gI, corresponding to VZV open reading frames (ORFs) 14 and 67, respectively, were required for the establishment of latency in this model. A VZV gI deletion mutant (DeltagI) derived from a recombinant Oka (rOka) cosmid and a gC null mutant obtained from a clinical isolate were inoculated into the footpads of 6-week-old rats, and the presence of viral DNA and eight different VZV RNA transcripts corresponding to the three classes of genes was investigated by in situ RT-PCR amplification and in situ hybridization (ISH) in the DRG at 1 week, 1 month, and 18-24 months after infection.

Absence of detection of varicella-zoster virus DNA in temporal artery biopsies obtained from patients with giant cell arteritis.

It has been suggested that Varicella-Zoster virus (VZV) may play a role in the pathogenesis of giant cell arteritis (GCA). We therefore used both in situ hybridisation and in situ Polymerase Chain Reaction amplification techniques in an attempt to identify VZV DNA in 15 temporal arteries from histologically proven GCA. We did not detect evidence of VZV DNA in the arteries of any of these subjects, nor in temporal arteries obtained from seven normal control subjects.

Varicella-zoster virus gene 66 transcription and translation in latently infected human Ganglia.

Latent infection with varicella-zoster virus (VZV) is characterized by restricted virus gene expression and the absence of virus production. Of the approximately 70 predicted VZV genes, only five (genes 4, 21, 29, 62, and 63) have been shown by multiple techniques to be transcribed during latency. IE62, the protein product of VZV gene 62, is the major immediate-early (IE) virus-encoded transactivator of viral gene transcription and plays a pivotal role in transactivating viral genes during lytic infection.