The influence of chronic stress on multiple opioid peptide systems in the rat: pronounced effects upon dynorphin in spinal cord

Recurrent exposure to intermittent electrical foot-shock (30 min, twice daily) for 7 days caused an increase in immunoreactive (ir) dynorphin and ir-alpha-neo-endorphin in lumbar and cervical (but not thoracic) spinal cord as measured 16 h following the final session. At this time the level of ir-Met-enkephalin-Arg6-Gly7-Leu8 (MEAGL) was also increased at the lumbar level. An acute foot-shock depleted spinal cord dynorphin in chronically stressed but not in naive rats. No alterations in levels of ir-dynorphin or ir-MEAGL were seen in discrete brain tissues. In contrast to the brain, where no effects were seen, the levels of beta-endorphin increased in both lobes of the pituitary. This change, however, was not accompanied by an alteration in levels of beta-endorphin in plasma. These data show that chronic foot-shock stress selectively influences particular pools of opioid peptides, predominantly those derived from proenkephalin B in the spinal cord and from proopiomelanocortin in the anterior pituitary. It is suggested that alterations observed in the spinal cord reflect enhanced activity of the proenkephalin B system in response to chronic nociceptive stimulation.     

Endoscopic ligation of esophageal varices for prophylaxis of first bleeding in children and adolescents with portal hypertension: preliminary results of a prospective study

Background/purpose

Endoscopic variceal ligation (EVL) is effective in controlling rebleeding from esophageal varices in children, but there is no data on the use of EVL to prevent initial bleeding. The objective of this study was to prospectively evaluate the efficacy of EVL in preventing the first hemorrhage from esophageal varices in children.

Methods

Thirty-seven children with portal hypertension (22 liver cirrhosis, 15 portal vein thrombosis), aged 4 to 17 years (M = 9.5 ± 4.4 years) were included in the study. The criteria for inclusion were (1) no previous variceal bleeding; (2) the presence of esophageal varices classified grade II or more, and (3) their enlargement by at least I grade after 6 months of observation without endoscopic treatment or appearance of endoscopic signs of high bleeding risk. A Multi-Band Ligator was used, and 2 to 6 bands were fixed under general anesthesia during one procedure depending on the number and size of varices. Follow-up examinations were performed every 3 months, repeating the procedure if necessary. In total, 75 procedures of EVL were performed, from one to 5 in each patient

Results

Four patients underwent liver transplantation before eradication of varices. Two others were excluded from the observation because of lack of compliance to the protocol. Of the remaining 31 patients, eradication of varices was achieved in 28 children (90.3%) after 2.0 EVL sessions performed at 3-month intervals. The average time of follow-up after cessation of treatment is 16 months. No bleeding from varices occurred in any child during or after treatment. There were no differences in results between children with liver cirrhosis and portal vein thrombosis. Development of hypertensive gastropathy was observed in 2 children with one episode of bleeding. Recurrence of varices without bleeding occurred in 3 children after 12, 13, and 28 months from eradication.

Conclusions

The study results confirmed that endoscopic variceal ligation is a safe and highly effective procedure in children with portal hypertension, regardless of its etiology. Eradication of esophageal varices was followed by 16 months free of bleeding. Prolonged observation is mandatory to conclude if preventive EVL influences the natural history of disease and diminishes the risk of first bleeding onset.     

Radio-opaque polyethylene for personalized craniomaxillofacial implants

Objective

This study aimed to present a new possibility to create radio-opaque implant material for craniomaxillofacial reconstruction.

Materials and methods

The test disks made of the own compound of polyethylenes with addiction of 2, 4, and 6 % of weight TiO₂ was investigated for cytotoxicity [each group 15 disks respectively]. Next, computed tomography of the disks was performed in environment of muscle and fat. Hardness, tensile modulus and strength, and compressive modulus and strength were tested too.

Results

Deterioration of mechanical properties of the composites containing titanium dioxide was observed [hardness, tensile modulus and strength, compressive modulus and strength, respectively: 56.7 ± 1.6 shore D, 354 ± 52, 22.5 ± 1.3, 21.8 ± 1.1, and 2995 ± 327 MPa as addiction of 2 % TiO₂; 52.0 ± 0.9 shore D, 347 ± 66, 18.0 ± 0.7, 14.2 ± 0.9, and 1396 ± 477 MPa as 4 % TiO₂; 51.3 ± 1.3 shore D, 316 ± 9, 17.4 ± 0.2, 13.6 ± 0.6, and 1100 ± 144 MPa as 6 % TiO₂ added]. The test disks revealed no cytotoxicity effect on human osteoblasts. The new material presents mild radio-opacity which was enough to observe the implant in relation to fat and muscle, but with no visible effect of beam hardening.

Conclusion

In view of the performed tests, the polyethylene enriched by titanium dioxide seems to be a proper material to consider manufacturing of craniomaxillofacial implants.

Clinical relevance

Maxilloafacial surgery is still looking for new implantologic materials. The proposed one is a new way to manufacture an implant visible in computed tomography which does not interfere with its shape in radiological examination and makes it possible to observe the surrounding soft tissues.

     

Tapentadol – A representative of a new class of MOR-NRI analgesics

Tapentadol is a centrally acting analgesic with a dual mode of action as a μ-opioid receptor (MOR) agonist and a noradrenaline reuptake inhibitor (NRI). It was initially approved by the US Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients, and in August 2011, for chronic pain in an prolonged release form in the same population. Due to its limited protein binding capacity, the absence of active metabolites and significant microsomal enzyme induction or inhibition, tapentadol has a limited potential for drug–drug interactions. It appears to be well-tolerated and effective in the treatment of moderate-to severe acute and chronic pain. Owing to its dual mechanism of action, it is hypothesized to be good option in the treatment of both nociceptive and neuropathic pain.     

Colorectal carcinoma in Poland in 1975 and 1995: not only more,but also different

BACKGROUND AND AIMS: We previously reported that the sole clinicopathological parameters of carcinomas diagnosed in a single institution in 1975 differed from those in patients diagnosed in 1995. The findings might be compatible with the loss of importance of the microsatellite instability of the carcinogenic pathway. MATERIALS AND METHODS: We examined the microsatellite status and selected immunomarkers (Ki-67, p53, BAX) in the archival material from 1975 (n=76) and 1995 (n=105). RESULTS AND CONCLUSION: The distribution of tumors showing no microsatellite instability, low microsatellite instability, and high microsatellite instability in the 2-yearly cohorts was similar (1975: 55.6%, 22.2%, 22.2%; 1995: 60.2%, 20.4%, 19.4%, respectively). The percentage of carcinomas showing microsatellite instability at the APC locus differed significantly (1975: 37.5%; 1995: 21.4%). The typical clinicopathological parameters of carcinomas exhibiting high microsatellite instability were largely shared by the carcinomas demonstrating instability at the APC locus. The carcinomas resected in 1995 more frequently demonstrated high expression of an antiapoptotic protein BAX and a different distribution of their Ki-67 proliferation fraction. The evolution of colorectal carcinoma in Poland also involves qualitative changes, including its genetic background.