Intrathecal beta-funaltrexamine antagonizes intracerebroventricular beta-endorphin- but not morphine-induced analgesia in mice

We have reported previously that beta-endorphin and morphine administered supraspinally produce analgesia by activating different descending pain inhibitory systems in rats. The descending system activated by beta-endorphin involves a spinal endorphinergic system whereas the descending system activated by morphine does not. To determine if this differential action of intraventricular beta-endorphin and morphine also occurs in mice, the effects of pretreatment with intrathecal (i.t.) and i.c.v. beta-funaltrexamine (beta-FNA) on analgesic response induced by i.c.v. and i.t. beta-endorphin and morphine were studied in mice. beta-FNA (2.5 micrograms) was injected i.t. or i.c.v. 24 hr before beta-endorphin or morphine administration and hot-plate and tail-flick responses were measured. Intrathecal beta-FNA attenuated i.c.v. beta-endorphin- but not i.c.v. morphine-induced analgesia. On the other hand, i.t. beta-FNA blocked both i.t. beta-endorphin- and morphine-induced analgesia, but was more effective in blocking the effects of i.t. morphine than beta-endorphin. At the supraspinal sites, beta-FNA administered i.c.v. was found to antagonize i.c.v. morphine-induced analgesia but not i.c.v. beta-endorphin-induced analgesia. The present results in mice are consistent with previous studies in rats and indicate that beta-endorphin and morphine activate different supraspinal opioid receptors. Also, analgesia produced by these two opioids resulted from activation of different descending pain inhibitory systems. The spinal endorphinergic system was involved in the production of i.c.v. beta-endorphin-, but not morphine-induced analgesia.     

Defective platelet-fibrinogen interaction in hereditary canine thrombopathia

A unique, intrinsic, hereditary canine platelet disorder attributable to abnormal fibrinogen receptor availability is described. Thrombopathic platelets from 13 severely affected basset hounds failed to aggregate in response to all agonists tested except thrombin. Normal platelet interaction with the various stimuli was inferred on the basis of their ability to elicit unimpaired shape change in thrombopathic platelets. No quantitative differences in major platelet membrane glycoproteins, intraplatelet fibrinogen, adenine nucleotides, or serotonin uptake were detected. Dense granule secretion was impaired. The ultrastructural appearance of thrombopathic platelets was normal. Fibrinogen-platelet interaction was evaluated by reacting platelet-rich plasma (PRP) with fibrinogen coupled to polymeric acrylonitrile beads and scoring the extent of stimulus-induced agglutination. The aggregatory responses of normal and thrombopathic platelets were closely correlated with fibrinogen receptor availability. In contrast to human platelets, epinephrine-stimulated canine platelets did not interact with immobilized fibrinogen, and arachidonate generally induced only weak agglutination. Thrombopathic platelets agglutinated fibrinogen beads at reduced rates when stimulated with physiologic doses of thrombin and high-dose calcium ionophore, A23187. Our data suggest that thrombin-mediated induction of canine platelet fibrinogen receptors may proceed by pathway(s) alternate to those shared by other platelet agonists, and/or that secreted granule constituents may act synergistically with thrombin to overcome inhibition of signal-response- coupled reactions mediating the interaction of fibrinogen with its receptor. This congenital platelet defect provides further evidence, in a species other than human, for the pivotal role of fibrinogen receptor induction in platelet aggregation.     

A prospective study of the risk factors associated with failure of mini-implants used for orthodontic anchorage

PURPOSE: The aim of this prospective clinical study was to assess the risk factors associated with failure of mini-implants used for orthodontic anchorage. MATERIALS AND METHODS: A total of 140 mini-implants in 44 patients, including 48 miniplates and 92 freestanding miniscrews, were examined in the study. A variety of orthodontic loads were applied. The majority of implants were placed in the posterior maxilla (104/140), and the next most common location was the posterior mandible (34/140). RESULTS: A cumulative survival rate of 89% (125/140) was found by Kaplan-Meier analysis. There was no significant difference in the survival rate between miniplates and freestanding miniscrews, but miniplates were used in more hazardous situations. The Cox proportional-hazards regression model identified anatomic location and peri-implant soft tissue character as 2 independent prognostic indicators. The estimated relative risk of implant failure in the posterior mandible was 1.101 (95% confidence interval, 0.942 to 1.301; P = .046). The risk ratio of failure for implants surrounded by nonkeratinized mucosa was 1.117 (95% confidence interval, 0.899 to 1.405; P = .026). DISCUSSION AND CONCLUSION: The results confirmed the effectiveness of orthodontic mini-implants, but in certain situations adjustment of the treatment plan or modifications in the technique of implant placement may lead to improved success rates.     

The analgesic efficacy of ibuprofen in periodontal surgery: A multicentre study

The efficacy of a non-steroidal anti-inflammatory agent, ibuprofen, was evaluated in pain control following periodotal surgery. This type of agent acts peripherally by inhibiting the release of prostaglandins and minimizing the local inflammatory response. Thus there may be an advantage in pre-treatment administration of the drug so as to delay or even prevent postoperative pain.
The study was multicentre, involving a Public Hospital Periodontal Unit, two specialist periodontal practices in Sydney, NSW, ad two in Canberra, ACT. One hundred and twenty-seven pateints who were to undergo periodontal surgery were randomly given either two 200 mg tablets of ibuprofen or two matching placebo tablets at least 30 minutes before administration of local anaesthesia. The procedure was double blind: neither the patient nor the colinical was aware of the tablet identity.
Postoperatively, all patients were given labelled ibuprofen for pain relief, but were randomly divided into two groups: As directed who were instructed to take the drug regularly for two days postoperatively, and As required , who were to take the drug only if needed for pain relief. All patients completed a diary recording quantity and time of medication, and regular assessment of pain experience utilizing a viaual analogue scale.
The As directed group showed no significant difference in pain experience between pre-operative and post-operative only medication, but the As required group experienced significantly less pain and requirement for medication if the ibuprofen was administered pre-operatively.     

Calcium current restitution in mammalian ventricular myocytes is modulated by intracellular calcium

Restitution of the conventional L-type calcium current (ICa) was studied in dog or guinea pig ventricular myocytes to understand its time course and regulation. Whole-cell ICa free of other overlapping currents was recorded with a suction pipette. The intracellular environment was varied by intracellular dialysis. The properties of ICa were similar in dog and guinea pig ventricular myocytes, except that the amplitude of ICa was larger in the latter (2.2 +/- 0.5 nA in guinea pig cells and 0.9 +/- 0.2 nA in dog cells, n = 8 for both). In both types of cells during restitution a holding voltage (Vh) negative to -50 mV induced a transient increase in ICa above the control level (ICa overshoot). This overshoot was inhibited by substituting barium for calcium, lowering [Ca]0, increasing intracellular calcium buffering capacity, ryanodine (1-2 microM), or caffeine (10 mM). The overshoot peaked 30-100 msec after repolarization from the conditioning depolarization and gradually declined over the following 2-3 seconds. During the overshoot, although the amplitude of ICa was larger its half-time of decay was longer than the control. The maximum overshoot occurred following a conditioning step to plateau voltages and it was decreased by prolonging the conditioning step from 50 to 100 or 500 msec. It is concluded that intracellular calcium regulates restitution of the L-type calcium channels in mammalian ventricular myocytes and that the sarcoplasmic reticulum is involved in this process.     

Peripheral Lymphocyte Subpopulations in Patients with Herpes Genitalis

Peripheral blood samples from 52 women including 16 with herpes genitalis and 36 healthy persons were studied to enumerate subpopulations of lymphocytes. T lymphocyte counts were done by SRBC rosette tests and B lymphocytes by immunobead rosette tests using antibody-coated polyacrylamide beads. It was found that the mean percentage of «active T lymphocytes was significantly less in the patients with herpes genitalis than in the controls (herpes genitalis; 13.9 ± 6.8%, controls; 25.0 ± 8.3%, p < 0.001). No difference was noted in the percentage of «total» T lymphocytes, «total» B lymphocytes and subsets of B lymphocytes (IgG-, IgA- and IgM-bearing lymphocytes) between the patients and controls. The present findings suggest that cell-mediated immune function associated with «active» T lymphocytes is suppressed in patients with herpes genitalis.     

Possible muscarinic regulation of catecholamine secretion mediated by cyclic GMP in isolated bovine adrenal chromaffin cells

Catecholamine secretion and cyclic GMP levels were measured in chromaffin cells isolated from bovine adrenal medulla. Acetylcholine (ACh) and nicotine, but not muscarine, induced 8- to 10-fold increases in catecholamine secretion, with respective ED₅₀ values of 10 and 2 M. Cyclic GMP levels were also increased from 3- to 5-fold in the presence of ACh, and this stimulation was mimicked by muscarine but not by nicotine. Half-maximum stimulations of cyclic GMP levels with ACh and muscarine were observed at 0.1 and 0.3 M respectively. The order of potency of various cholinergic drugs for cyclic GMP stimulation was as follows: ACh > oxotremorine > methacholine > muscarine > carbamylcholine > furthretonium > arecholine > bethanechol. Pilocarpine, McN-A-343, and AHR-602 were inactive at concentrations between 10^?8 and 10^?3 M. Isobutylmethylxanthine (1 mM), a specific phosphodiesterase inhibitor, caused a 7-fold increase in cyclic GMP and potentiated 3-fold the stimulation of cyclic GMP by ACh. The nicotine-induced catecholamine secretion was inhibited 19 and 33 per cent by the co-stimulation of the muscarinic receptor with 0.2 and 0.5 M ACh, respectively. Isobutylmethylxanthine (1 mM) also caused a 44 per cent inhibition of nicotine-induced catecholamine secretion, and its effect was additive to that of ACh. Atropine (0.1 M) selectively abolished the inhibition caused by ACh. Similar inhibitions were also obtained in the presence of exogenous dibutyryl cyclic GMP or 8-bromo cyclic GMP. These data indicate that the nicotinic stimulation of catecholamine secretion from bovine adrenal chromaffin cells may be regulated by cyclic GMP via the stimulation of a muscarinic receptor.     

Biochemical alterations in livers of rats exposed to vinyl chloride.

Sprague-Dawley rats were exposed to vinyl chloride to determine the earliest sequential biochemical changes occurring with liver injury before anglosarcoma development. Activity of glucose-6-phosphatase, a key gluconeogenic enzyme in the liver microsomal fraction, decreased 25% with respect to controls after 70 h of exposure. Glucose-6-phosphate dehydrogenase activity increased twofold after more than 100 h of exposure. Nonprotein sulfhydryl levels (glutathione and/or cysteine) showed a slight but progressive elevation, whereas glutathione reductase activity increased 50-60% during exposure to vinyl chloride.NADPH-cytochrome c reductase and mixed function oxidase were unchanged in the same microsomal fraction. There markers of liver mitochondrial, cytosol, and microsomal function. No significant histological changes were found on light microscopic examination during this exposure period. However, with electron microscopy, dilation of rough endoplasmic reticulum was seen in the animals exposed for more than 137 h. These enzymatic changes are considered to reflect early hepatocellular adaptation to vinyl chloride exposure with very mild or limited hepatocellular injury in its earliest stage.     

Identification of Merkel cell polyomavirus in Merkel cell carcinoma tissue: case report of a Taiwanese patient

Merkel cell carcinoma (MCC) is a rare malignancy with aggressive behavior mostly seen in the elderly and immunosuppressed patients. In 2008, the clonal integration of a new human polyomavirus, named Merkel cell polyomavirus (MCPyV), was found to be closely associated with the development of MCC. This correlation was established by subsequent reports, mostly in Caucasians. To evaluate whether this correlation is also relevant among the Taiwanese population, we used polymerase chain reaction to detect the presence of MCPyV in a formalin-fixed and paraffin-embedded MCC specimen. In addition, we used tissue with seborrheic keratosis from the same patient as a control. Three different specific primer sets, LT1, LT3 and VP1, were used to amplify characteristic MCPyV genes, and large T antigen and VP1 genes, respectively. Amplicons of the expected sizes for all three primer pairs were detected in MCC tissue and amplicons for both LT3 and VP1 were detected in seborrheic keratosis tissue. More studies are needed to quantify viral positivity of MCPyV in various tissues of patients with MCC and to establish genetic interactions between the virus and host.