Changes in the brain kappa-opioid receptor levels of rats in withdrawal from physical dependence upon butorphanol

Changes in kappa-opioid receptor levels have been implicated in the development of physical dependence upon and withdrawal from the mixed agonist-antagonist opioid, butorphanol. Immunoblotting analysis was performed to determine the levels of kappa- and mu-opioid receptors in brain regions of rats in withdrawal from dependence upon butorphanol or morphine. Physical dependence was induced by a 72 h i.c.v. infusion with either butorphanol or morphine (26 nmol/microl/h). Withdrawal was subsequently precipitated by i.c.v. challenge with naloxone (48 nmol/5 microl/rat), administered 2 h following cessation of butorphanol or morphine infusion. Immunoblotting analysis of kappa-opioid receptors from butorphanol-withdrawal rats showed significant increases in 11 of 21 brain regions examined, including the nucleus accumbens, amygdala, dorsomedial hypothalamus, hypothalamus, paraventricular thalamus, thalamus, presubiculum, and locus coeruleus, when compared with saline treated, non-dependent controls. In addition, significant reductions were found in the hippocampus and in cortical brain regions, including the parietal cortex and temporal cortex from butorphanol-withdrawal rats. These findings contrasted with those from morphine-withdrawal rats, in which the only changes noted were increases in the thalamus and paraventricular thalamus. Changes in the levels of the mu-opioid receptor protein were observed in 11 of 21 brain regions examined in morphine-withdrawal rats, but only in three of 21 in butorphanol-withdrawal rats. These results implicate a substantive and largely unique role for kappa-opioid receptors in mediation of the development of physical dependence upon, and the expression of withdrawal from, butorphanol, as opposed to the prototypical opioid analgesic, morphine.     

Metabolic Syndrome,Diabetes, and Cardiovascular Risk in HIV

HIV infection and its treatment have been associated with adipose tissue changes and disorders of glucose and lipid metabolism. The proportion of HIV-infected adults over the age of 50 is also growing placing HIV-infected adults at particular risk for metabolic perturbations and cardiovascular disease. The metabolic syndrome in HIV-infected adults has been increasingly studied but whether HIV is associated with greater risk remains unclear, likely because of the interplay of host, viral and antiretroviral factors that are associated with the components of the metabolic syndrome. The relationship between HIV and diabetes mellitus (DM) risk has also been debated. While the Framingham Risk Score is a well-accepted measure of 10-year cardiovascular risk in the general population, it may not accurately predict risk in the HIV setting due to HIV-related factors such as inflammation that are not accounted for. We summarize the recent literature on metabolic syndrome, DM, and cardiovascular risk in HIV-infected adults.     

In vivo testing of nanoparticle-treated TTCP/DCPA-based ceramic surfaces

This study reports the development of a non-dispersive calcium phosphate cement (nd-CPC) paste containing tetracalcium phosphate and anhydrous dicalcium phosphate that can be used as a filling material in dental and orthopedic applications. The nd-CPC bone cement is compared with two commercial materials, OsteoSet^® and Collagraft^® bone grafts. Gross examination of retrieved implants/bone composite samples indicated that none of the implants in this study evoked an inflammatory response. The OsteoSet^® (calcium sulfate) implant was resorbed too quickly to allow for osteo-remodeling, and it led to the formation of fibrous connective tissue in the fracture site, which remained even 24 weeks after implantation. Histological examination revealed that nd-CPC and Collagraft^® (hydroxyapatite/tricalcium phosphate/collagen) had greater remodeling and osteoconductive activity than OsteoSet^® at both 12 and 24 weeks after implantation. Greater remodeling activities were found with nd-CPC cement than with the other materials at 12 weeks after implantation, and the Fourier transform infrared absorption band of carbonate or cellulose derivatives grew from 6 weeks to 24 weeks after implantation in nd-CPC cement. These findings show that nd-CPC compares favorably to commercial bone remodeling materials, and the fact that it is in a paste formulation makes it an ideal material to fill regeneration defects.     

Influenza A H5N1 and HIV co-infection: case report

Background  

The role of adaptive immunity in severe influenza is poorly understood. The occurrence of influenza A/H5N1 in a patient with HIV provided a rare opportunity to investigate this.     

A composite graft material containing bone particles and collagen in osteoinduction in mouse.

Demineralized allogenic bone matrices (DABM) and demineralized freeze-dried bone allograft (DFDBA) have been successfully used as bone-graft materials in the treatment of acquired and congenital cranio-maxillofacial defects and in some orthopedic surgery. However, these bone-graft "powders" have many shortcomings. For example, placement of particulate graft material in a hemorrhaging site can result in inadequacies or inaccurate attachment as well as loss of the graft materials. To minimize the inadequacies of powderlike graft materials, xenogenic collagen isolated from human tendon, skin, or bone was added to the bone-graft particles to form a composite spongelike implant. This material is commercially available and consists of 60% collagen and 40% DFDBA (DynaGraft, GenSci Co., Irvine, CA). The goal of this study was to evaluate the characteristics of composite graft implants in the mineralization process in an animal model in comparison with DFDBA powder and pure collagen. Seventy-two Swiss Webster mice were divided into three groups: an experimental group implanted with DynaGraft, two comparison groups implanted with either DFDBA or collagen only. All the graft materials were surgically implanted and inserted into the left thigh muscle. Mice were humanely killed at 1, 2, 3, 4, 6, 8, and 12 weeks. Then the muscle tissues in the vicinity of the implants were excised and processed for histology. Paraffin sections were stained with hematoxylin and eosin (H&E), the Von Kossa method, and Masson's trichrome. Some selected specimens were processed for transmission electron microscopic observation. After 1 week of implantation, the DynaGraft group showed calcium deposition on the collagen material and on the periphery of the DFDBA particles. Increased calcification and bone-forming cells were observed at 4-6 weeks. After 8 weeks, the implant formed a calcified nodule and only heavily mineralized connective tissue was observed at the implanted site. The group implanted with DFDBA powder showed calcification around the particulates. The collagen-sponge control group revealed no calcification or bone formation during the period of implantation. The light microscopic findings were confirmed by electron microscopy. Quantitative radiographic density DynaGraft and DFDBA graft followed sequentially over a period 120 days. It was concluded that a higher rate of calcification and bone formation was produced in the composite graft implant compared to the DFDBA implant. The composite graft material (DynaGraft), which contains both collagen and DFDBA, proved to be more effective for bone formation than particle components alone.     

Exon 33 T/T genotype of the thyroglobulin gene is a susceptibility gene for Graves’ disease in Taiwanese and exon 12 C/C genotype protects against it

This study investigates whether Tg gene polymorphisms can be associated with Graves’ disease (GD) in a Taiwanese population and identifies potential polygenic susceptive genes for GD. The findings of such a study may have important implications for prognostic prediction and treatment of GD. We performed case control association studies for the 3 discovered Tg single nucleotide polymorphisms (SNPs) (E10, E12, E33) in 215 GD patients and 141 controls. The three SNPs were identified within the Tg gene. These SNPs were analysed by a fluorescent-based restriction fragment length polymorphism method (RFLP) and PCR. The genotype and allele frequencies at E10SNP158, E12SNP and E33SNP in GD patients were compared with those of the controls. In addition, we analysed the interactions between these SNPs and the clinical and laboratory variables. We found a significant difference in the T/T genotype of E33SNP and G/G genotype of E12SNP compared with the control group (p < 0.001). We also found the E33SNP T/T genotype to be positively associated with development of GD, whereas the E12SNP G/G genotype protected it.