Novel approach to demonstrate high efficacy of μ opioids in the rat vas deferens: A simple model of predictive value

14-O-Methyloxymorphone and 14-methoxymetopon were reported as highly selective and potent μ opioid receptor agonists. The aim of this study was to demonstrate the opioid activity of these compounds in vitro and in vivo in comparison to oxymorphone, morphine and DAMGO. The μ opioid receptor efficacy, full or partial agonist nature of opioids was analyzed in the rat vas deferens (RVD) bioassay. Compared to oxymorphone, 14-O-methyloxymorphone and 14-methoxymetopon showed greater affinities to the rodent brain μ opioid receptors in receptor binding assays. In isolated organs 14-O-methyloxymorphone and 14-methoxymetopon were 3-10-fold more potent than the μ agonist opioid peptide, DAMGO. All tested compounds reached at least 70% maximum inhibition in mouse vas deferens (MVD) except morphine and oxymorphone. In the RVD, morphine could not exceed 50% inhibition of the twitches while 14-O-methyloxymorphone and 14-methoxymetopon showed inhibitory effects more than 70%. Oxymorphone reached only 4% maximal agonist effect and antagonized the inhibitory effect of DAMGO. The investigated morphinans produced dose-dependent antinociceptive activities in mice and rats. Both, 14-O-methyloxymorphone and 14-methoxymetopon are highly efficacious μ opioid receptor agonists in the RVD exhibiting full μ agonist properties. The RVD tissue contains μ receptors indicated by the comparable K_e values of the μ antagonist naltrexone against DAMGO in the MVD. RVD may be a good alternative to assess the μ receptor efficacy of opioid agonists providing a more physiological environment for the ligand-receptor interaction than other efficacy measuring methods such as the [³⁵S]GTPγS binding assay.     

Synthesis and antinociceptive activities of some pyrazoline derivatives

In the present study, some pyrazoline derivatives were synthesized to investigate their potential antinociceptive activities. 1-[(Benzoxazole/benzimidazole-2-yl)thioacetyl]pyrazoline derivatives were obtained by reacting 3,5-diaryl-1-(2-chloroacetyl)pyrazolines with 2-marcaptobenzoxazole/benzimidazole. The chemical structures of the compounds were elucidated by IR, (1)H NMR and FAB(+)-MS spectral data and Elemental Analyses. All of the compounds (100 mg/kg) exhibited significant antinociceptive activities in both hot plate and acetic acid-induced writhing tests. Naloxone (5 mg/kg) pre-treatment reversed the antinociceptive activities suggesting the involvement of opioid system in the analgesic actions. None of the compounds impaired motor coordination of animals when assessed in the Rota-Rod model. These results support the previous papers reporting the opioid sensitive antinociceptive activities of various benzoxazole/benzimidazole-pyrazoline derivative compounds.     

Soft tissue augmentation for restoration of facial contour deformities using the free SCIA/SIEA flap

Reconstruction for facial contour deformities is still a challenging process and treatment for most cases is achieved only by soft tissue augmentation. The use of free tissue transfer offers the advantage of one step vascularized soft tissue augmentation. This article summarized the authors' use of de-epithelialized free superficial circumflex iliac artery/superficial inferior epigastric artery flap for facial contour deformities. Of these patients, two had hemifacial microsomia, one depressed scar, and one had hemifacial progressive atrophy. Stable restoration of the facial contour was achieved in all patients. The advantages of this flap are numerous. Two surgical teams may work at the same time for flap harvesting and recipient area preparation. A wide flap may be planned for large contour deformity to achieve one single stage augmentation. Pedicle course of this flap allows primary de-fating without disturbing distal flap circulation when in need of a thin flap for mild contour deformity. Donor site may be closed with bikini (abdominoplasty) incision, which has excellent esthetic outcome compared to other flaps.     

Effects of erythropoietin on reducing brain damage and improving functional outcome after traumatic brain injury in mice

OBJECT: This study was designed to investigate the beneficial effects of recombinant human erythropoietin (rhEPO) treatment of traumatic brain injury (TBI) in mice. METHODS: Adult male C57BL/6 mice were divided into 3 groups: 1) the saline group (TBI and saline [13 mice]); 2) EPO group (TBI and rhEPO [12]); and 3) sham group (sham and rhEPO [8]). Traumatic brain injury was induced by controlled cortical impact. Bromodeoxyuridine (100 mg/kg) was injected daily for 10 days, starting 1 day after injury, for labeling proliferating cells. Recombinant human erythropoietin was administered intraperitoneally at 6 hours and at 3 and 7 days post-TBI (5000 U/kg body weight, total dosage 15,000 U/kg). Neurological function was assessed using the Morris water maze and footfault tests. Animals were killed 35 days after injury, and brain sections were stained for immunohistochemical evaluation. RESULTS: Traumatic brain injury caused tissue loss in the cortex and cell loss in the dentate gyrus (DG) as well as impairment of sensorimotor function (footfault testing) and spatial learning (Morris water maze). Traumatic brain injury alone stimulated cell proliferation and angiogenesis. Compared with saline treatment, rhEPO significantly reduced lesion volume in the cortex and cell loss in the DG after TBI and substantially improved recovery of sensorimotor function and spatial learning performance. It enhanced neurogenesis in the injured cortex and the DG. CONCLUSIONS: Recombinant human erythropoietin initiated 6 hours post-TBI provided neuroprotection by decreasing lesion volume and cell loss as well as neurorestoration by enhancing neurogenesis, subsequently improving sensorimotor and spatial learning function. It is a promising neuroprotective and neurorestorative agent for TBI and warrants further investigation.     

Non-convulsive status epilepticus following antibiotic therapy as a cause of unexplained loss of consciousness in patients with renal failure

Background  Non-convulsive status epilepticus (NCSE): a condition that may be associated with different levels of altered consciousness without any apparent motor signs. There are published reports that it may be associated with antibiotic use patients with renal failure. Method  This is a retrospective analysis of our 12 NCSE (2 men, 10 women, a mean age: 58.4 ± 17.5 range of 29–85 years) patients with renal failure who have used antibiotics. Results  Twelve patients were receiving a total of 19 antibiotics including mainly beta-lactams. The mean duration of time between start of antibiotic treatment and NCSE was 8.0 (3–21) days. In all of the patients, neurological symptoms were slowly progressive and consisted of depression of consciousness and/or disorientation. Diazepam administration resulted in marked reduction or completely disappears of epileptic activity. Four of 12 patients (33%) died, but none of were associated with NCSE but primarily associated with infection developed secondary to the preexisting disease and with congestive heart failure which patients already had. Conclusion  Antibiotics, especially beta-lactams could be neurotoxic and may cause of NCSE. NCSE should be considered in patients with unexplained loss of consciousness; EEG must be a part of investigations in patients with uraemia receiving antibiotics.     

Fibrin ring granuloma in chronic hepatitis C: virus-related vasculitis and/or immune complex disease?

Fibrin ring granulomas are rare lesions whose pathophysiology has remained somewhat elusive. It has been suggested that these peculiar lesions are related to focal vasculitis with endothelial injury and deposition of immune complexes. Fibrin ring granulomas have been described in Q fever; in viral infections such as cytomegalovirus, Epstein-Barr virus, and hepatitis A virus; and in other conditions. We submit the first reported case of fibrin ring granuloma in a patient with chronic hepatitis C infection, in whom other potential etiologies have been excluded, and offer a brief review of available literature on the pathogenesis of both conditions.     

Determination of hepatitis B virus DNA incidence, viral load, and mutations in blood donors with HBsAg and anti-HBs-negative serology and antibodies to hepatitis B core antigen

BACKGROUND: The aim of the present study was to determine hepatitis B virus DNA incidence, viral load, and mutations in blood donors with HBsAG and anti-HBs negative serology and antibodies to hepatitis B core antigen. METHODS: Blood samples were collected from 1000 blood donors with HBsAg-negative test results. Anti-HBc total screening was performed using the ELISA method. HBsAg-negative/anti-HBc total-positive samples were tested for anti-HBs, anti-HBc IgM, HBeAg, and anti-HBe. Samples with isolated anti-HBc were determined for viral load of HBV DNA using real-time PCR. RESULTS: Anti-HBc total was established as positive in 200 (20%) of the 1000 blood donors. While anti-HBs was negative in 59 (29.5%) of the 200 anti-HBc-positive samples, it was found to be positive in 141 (70.5%) of them. All of the other hepatitis B markers were negative in all of the anti-HBs-negative samples. HBV DNA was not detected in the sera of the isolated anti-HBc-positive blood donors with real-time PCR. CONCLUSION: Although we could not detect HBV DNA in the sera of the isolated anti-HBc-positive blood donors, findings in the literature suggest that anti-HBc testing should be used in combination with HBsAg for the screening of blood donors to reduce risk. After that, the most appropriate algorithm to follow can be HBV DNA screening of donors.