Effect of ethanol extract of Punica granatum L against Freund’s complete adjuvant-induced arthritis in rats

Purpose: To investigate the protective effect of ethanol extract of P. granatum against arthritis in rat model. Methods: Twenty-six adult male Wistar rats (120 - 150 g) were separated into four groups (n = 6): normal control, arthritic control and two treatment groups. With the exception of normal control group, arthritis was induced by intraplantar administration of Freund’s complete adjuvant (FCA) on the 1st day of drug administration. The arthritic control group was not treated, while the treatment groups received extract orally at 500 or 750 mg/kg for the period of 4 weeks and at the end of each week, paw volume, thermal hyperalgesia, arthritic score and mechanical nociceptive threshold were performed to assess arthritis. Biochemical indicators and inflammatory cytokines in serum were determined using standard procedures. Results: There was significant decrease in paw volume and arthritic score; paw withdrawal latency was enhanced in extract-treated groups, compared to arthritic control group (p < 0.05). Furthermore, ALT, AST and ALP levels, as well as RF and MDA activities decreased significantly with extract treatment, compared with arthritic control group (p < 0.05). Treatment with the extract attenuated the altered level of interleukin 1β (IL-1β) and TNF-α levels in arthritic rats. Histological examination showed that treatment with the extract significantly reversed histological changes induced by arthritis. Conclusion: The results reveal that the beneficial effect of ethanol extract of P. granatum against FCAinduced arthritis is due to its ability to reduce the levels of inflammatory cytokines

Benzoxime carbaldehyde prevents rheumatoid arthritis in a rat model by inhibition of oxidative damage

Purpose: To investigate the effect of benzoxime carbaldehyde (BXCD) on rheumatoid arthritis (RA) in a rat model.Methods: Thirty male Sprague-Dawley rats were assigned randomly to 5 groups (6 rats per group): normal control, RA, and three treatment groups. Rats in the normal control and RA groups received normal saline, whereas those in the three treatment groups were given 2, 5 or 10 mg/kg of BXCD daily for 30 days by intraperitoneal injection. Pressure pain was analysed using electronic pressure pain detector, while the expressions of interleukin (IL)-6, interleukin (IL)-1β, nuclear factor (NF)-κB p65 and tumor necrosis factor (TNF)-α in serum were determined using enzyme-linked immunosorbent assay (ELISA) kits.Results: Treatment of RA rats with BXCD for 30 days led to significant (p < 0.05) recovery in pain threshold. At a dose of 10 mg/kg, BXCD decreased pain threshold value to a level comparable to that in normal control rats, and decreased arthritis score to 1, relative to arthritis score of 16 in untreated animals. Malondialdehyde (MDA) level was 4-fold higher in untreated RA rats than in normal and BXCD-treated groups. BXCD treatment increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and blocked increases in the blood levels of IL-6, IL-1β, NF-κB p65 unit, and TNF-α. Western blot assay showed that BXCD treatment prevented increase in the level of cyclooxygenase-2 (COX-2) in RA rat tissues.Conclusion: These results indicate that BXCD prevents RA in a rat model via inhibition of expressions of inflammatory cytokines and decrease in oxidative stress. Thus, BXCD has a strong potential for the management of RA.Keywords: Rheumatoid arthritis, Pain threshold, Antioxidant enzymes, Inflammation, Inflammatory cytokine

The profile inter‐unit reliability

To assess the quality of health care, patient outcomes associated with medical providers (eg, dialysis facilities) are routinely monitored in order to identify poor (or excellent) provider performance. Given the high stakes of such evaluations for payment as well as public reporting of quality, it is important to assess the reliability of quality measures. A commonly used metric is the inter‐unit reliability (IUR), which is the proportion of variation in the measure that comes from inter‐provider differences. Despite its wide use, however, the size of the IUR has little to do with the usefulness of the measure for profiling extreme outcomes. A large IUR can signal the need for further risk adjustment to account for differences between patients treated by different providers, while even measures with an IUR close to zero can be useful for identifying extreme providers. To address these limitations, we propose an alternative measure of reliability, which assesses more directly the value of a quality measure in identifying (or profiling) providers with extreme outcomes. The resulting metric reflects the extent to which the profiling status is consistent over repeated measurements. We use national dialysis data to examine this approach on various measures of dialysis facilities.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155899/1/biom13167_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155899/2/biom13161-sup-0001-BiomarkerDesign_supplementary_pub.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155899/3/biom13167.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155899/4/biom13161-sup-0003-supmat.pd

Drug nanoparticles by emulsion-freeze-drying via the employment of branched block copolymer nanoparticles

A large percentage of drug compounds exhibit low water solubility and hence low bioavailability and therapeutic efficacy. This may be addressed by preparation of drug nanoparticles, leading to enhanced dissolution rate and direct use for treatment. Various methods have been developed to produce drug nanocrystals, including wet milling, homogenization, solution precipitation, emulsion diffusion, and the recently developed emulsion freeze-drying. The drawback for these methods may include difficult control in particles size, use of surfactants & polymer, and low ratio of drug to stabilizer. Here, biocompatible branched block copolymer nanoparticles with lightly-crosslinked hydrophobic core and hydrophilic surface groups are synthesized by the direct monomer-to-particle methodology, characterized, and then used as scaffold polymer/surfactant to produce drug nanoparticles via the emulsion-freeze-drying approach. This method can be used for model organic dye and different poorly water-soluble drugs. Aqueous drug nanoparticle dispersions can be obtained with high ratio of drug to stabilizer and relatively uniform nanoparticle sizes

Cerebrospinal fluid may mediate CNS ischemic injury

BACKGROUND: The central nervous system (CNS) is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF) that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult. METHODS: Lumbar spinal cord ischemia was induced in rabbits by cross-clamping the descending abdominal aorta for 1 h, 2 h or 3 h followed by 7 d of reperfusion. Prior to ischemia, rabbits were subjected to the following procedures; 1) CSF depletion, 2) CSF replenishment at 0 mmHg intracranial pressure (ICP), and 3) replacement of CSF with 8% albumin- or 1% gelatin-modified artificial CSF, respectively. Motor function of the hind limbs and histopathological changes of the spinal cord were scored. Post-ischemic microcirculation of the spinal cord was visualized by fluorescein isothiocyanate (FITC) albumin. RESULTS: The severity of histopathological damage paralleled the neurological deficit scores. Paraplegia and associated histopathological changes were accompanied by a clear post-ischemic deficit in blood perfusion. Spinal cord ischemia for 1 h resulted in permanent paraplegia in the control group. Depletion of the CSF significantly prevented paraplegia. CSF replenishment with the ICP reduced to 0 mmHg, did not prevent paraplegia. Replacement of CSF with albumin- or gelatin-modified artificial CSF prevented paraplegia in rabbits even when the ICP was maintained at 10–15 mmHg. CONCLUSION: We conclude that the presence of normal CSF may contribute to the vulnerability of the spinal cord to ischemic injury. Depletion of the CSF or replacement of the CSF with an albumin- or gelatin-modified artificial CSF can be neuroprotective

The Optimal Timing of Antiretroviral Therapy Initiation in HIV-Infected Patients with Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Trial

The optimal timing of antiretroviral therapy (ART) initiation in human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (HIV/CM) is controversial. We designed a clinical trial to inves-tigate the optimal timing for ART initiation in HIV/CM patients. This will be a multicenter, prospective, and randomized clinical trial. Each enrolled patient will be randomized into either the early ART arm or the deferred ART arm. We will compare the mortality and incident rates of immune reconstitution inflammatory syndrome between the two arms. We hope to elucidate the optimal timing for ART initiation in HIV/CM patients