The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats

Increasing evidence has indicated that activated glial cells releasing nociceptive factors, such as interleukins and chemokines, are of key importance for neuropathic pain. Significant changes in the production of nociceptive factors are associated with the low effectiveness of opioids in neuropathic pain. Recently, it has been suggested that CCL2/CCR2 signaling is important for nociception. Here, we studied the time course changes in the mRNA/protein level of CD40/Iba-1, CCL2 and CCR2 in the spinal cord/dorsal root ganglia (DRG) in rats following chronic constriction injury (CCI) of the sciatic nerve. Moreover, we examined the influence of intrathecal preemptive and repeated (daily for 7 days) administration of RS504393, CCR2 antagonist, on pain-related behavior and the associated biochemical changes of some nociceptive factors as well as its influence on opioid effectiveness. We observed simultaneous upregulation of Iba-1, CCL2, CCR2 in the spinal cord on 7th day after CCI. Additionally, we demonstrated that repeated administration of RS504393 not only attenuated tactile/thermal hypersensitivity but also enhanced the analgesic properties of morphine and buprenorphine under neuropathy. Our results proof that repeated administration of RS504393 reduced the mRNA and/or protein levels of pronociceptive factors, such as IL-1beta, IL-18, IL-6 and inducible nitric oxide synthase (iNOS), and some of their receptors in the spinal cord and/or DRG. Furthermore, RS504393 elevated the spinal protein level of antinociceptive IL-1alpha and IL-18 binding protein. Our data provide new evidence that CCR2 is a promising target for diminishing neuropathic pain and enhancing the opioid analgesic effects.     

Can we reduce morphine use in elderly,proximal femoral fracture patients using a fascia iliac block?

Proximal femoral fractures are becoming increasingly common with an ageing population. Many patients have multiple comorbidities increasing their risk of opiate complications. 40 consecutive patients presenting with a proximal femoral fracture to a trauma centre in the UK were given either a Fascia Iliaca Block (FIB) with oral analgesia or just oral analgesia to control their pre-operative pain. Numeric pain scores and morphine consumption were used as outcome measures. Patients receiving a FIB had significant reduction in their pain scores compared to patients only receiving oral pain relief. There was also a significant reduction in both the actual oral morphine taken and the renal calculated level of morphine products in the group receiving the FIB. Patients undergoing a FIB required almost 50 mg less oral morphine pre-operatively. Nerve blocks should be used routinely to help pre-operative pain in proximal femoral fracture patients and to reduce the amount of morphine products prescribed. This prevents potential opiate complications in a highly susceptible cohort of patients often suffering with impaired renal function as a co-morbidity.     

Double teeth: evaluation of 10-years of clinical material

The aim of the study was to evaluate 10-years of clinical material referring to the rare dental abnormality of double teeth. The study material consisted of case records, operation-books and radiographic or photographic documentation on patients treated in the Department of Oral Surgery, Silesian Medical University, Katowice, from the 1st of June 2000 to the 31st of May 2010. The following features were considered important: age and sex, the reason why the patient reported for treatment, general state of health, the time of recognition and type of double teeth, location of double teeth, complaints and disturbances connected with double teeth, types of radiographs, the radiographic and macroscopic appearance of double teeth and treatment method. Diagnoses were as follows: eight conrescent teeth, two fused teeth, two geminated teeth and one invaginated tooth. The anomaly of a deciduous tooth was referred to in one case only. Double teeth were most often seen in the region of maxillary incisors and molars but rarely in the mandible. The region of incisors was affected chiefly in children and the region of molars in adults. Double incisors are usually recognized prior to treatment whereas double molars as late as during their extraction. In many cases, neither intraoral radiographs nor pantomographs help to confirm double teeth or provide sufficient information to plan the treatment. In such a situation, CT or CBCT should be used in addition to imaging diagnostics. Double teeth among incisors are usually accompanied by occlusal disorders. Therefore the therapeutic management is conducted by a team, including orthodontists.     

Stem cells in colon cancer. A new era in cancer theory begins

Introduction  

Despite the various therapeutic combinations and the emergence of new targeted therapies, there is still no curative treatment for all stages of colorectal cancer. Through the query for the best possible combination and solution, a new theory approaching colorectal cancer as a stem cell disease appeared, with a continuously growing body of evidence supporting this idea. The inability to directly recognize cancer stem cells has led researchers to an attempt of distinguishing those using indirect markers.     

Granulocyte colony stimulating factor treatment of resistant thin endometrium in women with frozen-thawed blastocyst transfer

The aim of the study was to assess the granulocyte-colony stimulating factor (G-CSF) effect on unresponsive thin (<7 mm) endometrium in women undergoing frozen-thawed embryo transfer at the blastocyst stage. A total of 62 women with thin unresponsive endometrium were included in the study, of which, 29 received a G-CSF infusion and 33 who opted out of the study served as controls. Patients in both groups had similar endometrial thickness at the time of the initial evaluation: 6.50 mm (5.50-6.80) in the G-CSF and 6.40 mm (5.50-7.0) in the control group. However, after the infusion endometrial thickness increased significantly in the G-CSF group in comparison with the controls (p=0.01), (Δ) 0.5 (0.02-1.2) (p=0.005). In the G-CSF group endometrium expanded to 7.90 mm (6.58-8.70) while in the control group to 6.90 mm (6.0-7.75). Five women in each group conceived. The clinical pregnancy rate was 5/29 (17.24%) in the G-CSF treated group and 5/33 (15.15%) in the control group (p>0.05). The live birth rate was 2/29 (6.89%) in the G-CSF group and 2/33 (6.06%) in the control group (p>0.05). We concluded that G-CSF infusion leads to an improvement in endometrium thickness but not to any improvement in the clinical pregnancy and live birth rates. Until more data is available G-CSF treatment should be considered to be of limited value in increasing pregnancy rate. Abbreviations: G-CSF: granulocyte colony-stimulating factor; M-CSF: macrophagecolony-stimulating factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; FET: frozen embryo transfer; IVF: in vitro fertilization     

Test–Retest Reliability of Capability Measurement in the UK General Population

Although philosophically attractive, it may be difficult, in practice, to measure individuals' capabilities (what they are able to do in their lives) as opposed to their functionings (what they actually do). To examine whether capability information could be reliably self‐reported, we administered a measure of self‐reported capability (the Investigating Choice Experiments Capability Measure for Adults, ICECAP‐A) on two occasions, 2 weeks apart, alongside a self‐reported health measure (the EuroQol Five Dimensional Questionnaire with 3 levels, EQ‐5D‐3L). We found that respondents were able to report capabilities with a moderate level of consistency, although somewhat less reliably than their health status. The more socially orientated nature of some of the capability questions may account for the difference. © 2014 The Authors Health Economics Published by John Wiley & Sons Ltd.