Effects of Topical Application of Clonidine Cream on Pain Behaviors and Spinal Fos Protein Expression in Rat Models of Neuropathic Pain, Postoperative Pain, and Inflammatory Pain

Background: Clonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity.

Methods: Clonidine (30, 100, and 300 [mu]g/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity.

Results: In neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain.     

Endocrinology: High incidence of embryo transfer cancellations in patients with polycystic ovarian syndrome

This study was aimed at assessing the outcome of in-vitro fertilization(IVF) and embryo transfer in patients with polycystic ovariansyndrome (PCOS). The results of IVF and embryo transfer in PCOSpatients (PCOS group, 78 cycles of 26 patients) were comparedwith those of a control group (423 cycles in 202 patients withoutmale factor; age and ovarian stimulation protocol were matched).Although the pregnancy rate per transfer was not different inthe two groups of patients (25 versus 34%, PCOS versus controlgroup), the PCOS group had a significantly lower pregnancy rateper follicle aspiration (19 versus 31%, P < 0.05). A notableresult was a significantly higher incidence of embryo transfercancellations in the PCOS group (22 versus 8%, P < 0.01),which resulted from unpredictable failure of either oocyte recoveryor fertilization. The incidence of unexplained complete failureof fertilization was significantly higher in the PCOS group(18 versus 5%, P < 0.01). These results may reflect a reducedquality of the oocytes in the PCOS group, and there was a subgroupof PCOS patients who repeatedly produced poor results of treatment.Although the ovarian stimulation regimen best suited to PCOSpatients remains to be determined, special care should be takenduring ovarian stimulation, especially when the PCOS patientshad experienced unexplained failure of oocyte recovery or fertilizationin the previous treatment cycle(s).     

Cationic polymerization of styrenes by protonic acids and their derivatives, 2. Two propagating species in the polymerization by CF3SO3H

The bimodal molecular weight distribution (MWD) of the polymers and the polymerization rate in the cationic polymerization of styrene by CF₃SO₃H were studied under a variety of conditions. Both the decrease of the dielectric constant of the reaction mixture and the addition of a common-ion salt (Bu₄N⁺SO₃CF) reduced the polymerization rate and the formation of the higher molecular weight portion of the polymers (the high polymer). It appears that of the two propagating species the one which forms the high polymer is more ionically dissociated and more reactive in propagation. Salt effects indicate that in nitrobenzene the propagating species is a solvent-separated ion pair and/or a free ion. The effects of monomer concentration on the bimodal MWD have shown that there are different chain-breaking reactions for the two propagating species. The possibility that the monomer is complexed with one of the growing species is also discussed.     

Synthesis of block copolymers from 1-chloro-1-octyne and other acetylenes through their sequential living polymerization by MoOCl4?n-Bu4Sn?EtOH

Block copolymerizations of 1-chloro-1-octyne (1-ClO) with several substituted acetylenes were examined by means of living polymerization. o-(Trifluoromethyl)phenylacetylene (o-CF₃PA), o-(trimethylsilyl)phenylacetylene (o-Me₃SiPA), 1-chloro-2-phenylacetylene (1-ClPA), p-butyl-o,o,m,m-tetrafluorophenylacetylene (p-BuF₄PA), and tert-butylacetylene (t-BuA) were used as comonomers, and the MoOCl₄-n-Bu₄Sn-EtOH (mole ratio 1:1:1) catalyst, which is known to effect living polymerization of substituted acetylenes, was employed. When o-CF₃PA and 1-CIPA were the comonomers in combination with 1-CIO, block copolymers were exclusively obtained in both orders of monomer addition. In the cases of o-Me₃SiPA and p-BuF₄PA as comonomers, the copolymerizations initiated from 1-CIO produced block copolymers selectively, whereas the homopolymers of o-Me₃SiPA and p-BuF₄PA also formed if the order of monomer addition was reversed. The pair of 1-CIO and t-BuA did not selectively yield block copolymers irrespective of the order of monomer addition. Thus, block copolymerization occurred between 1-CIO and monomers that show high “livingness” and close reactivities.     

Andrology: Pentoxifylline-enhanced acrosome reaction correlates with fertilization in vitro

To evaluate the possible effect of pentoxifylline on the acrosomereaction (AR) and its correlation with in-vitro fertilization(IVF), sperm samples obtained from 51 patients who underwentIVF treatment were studied. Acrosome reactions were evaluatedas spontaneous, pentoxifylline-treated and calcium ionophore(A23187) induced, before and after treatment. The correlationof AR with fertilization in vitro in spermatozoa pre-treatedwith pentoxifylline was sought. In cases with failure or verylow fertilization rate (10%) in their previous trials, spermatozoaafter swim-up were treated before insemination. Spontaneousacrosome loss remained low even after treatment (mean ±SD: 8.18 ± 1.74%). Response to A23187 was enhanced significantly(P < 0.001) by pre-treatment with pentoxifylline in 33 controlcases (group A) in which fertilization in vitro was previouslysuccessful without this treatment. Patients with at least twoepisodes of failed fertilization were divided into two groups.In 11 cases (group B), the IVF rate was improved significantly(P < 0.001) by the treatment. This was not observed in sevencases (group C) in which the treatment induced no increase inIVF rate. We achieved nine (27.3%) pregnancies in group A andfive (45.4%) pregnancies in group B. This study demonstratedthat pentoxifylline enhanced A23187 induced the acrosome reactionand this effect was correlated with improvement in IVF rate.     

HLA-DRB1*1602 allele is positively associated with HPV cervical infection in Bolivian Andean women

Incidence of cervical cancer is high among Bolivian Andean women. Human papillomavirus (HPV) infection is known as the major risk factor of cervical cancer. The host immune system plays an important role in the outcome of HPV infection and associated malignancies. In order to study the immunogenetic background of Bolivian Andean women with regard to HPV infection status, we compared HLA class I and class II allele frequencies between 37 HPV positive and 68 HPV negative Bolivian women. Demographic variables, including distribution of Andean ethnicities, were similar in both groups. Comparison of HLA class I allele frequencies between both groups indicated no significant difference. In contrast, HLA class II DRB1*1602 allele, an Amerindian allele, was significantly higher in the HPV positive women compared with HPV negative controls (chi(2) = 5.2, p < 0.05, odds ratio = 3.17; 95% confidence interval = 1.4-8.8). HPV types present in the HPV positive group were HPV-18, -16, -31, -33, and -58. These results suggest that HLA class II DRB1*1602 may confer susceptibility to infection with genetically related HPV types. This is the first report of an HLA class II association with HPV infection in an Andean population.     

Effects of ortho-substituents on the living polymerization of phenylacetylenes by MoOCl4-based catalysts

Polymerization of phenylacetylenes (PAs) having various ortho-substituents were examined by using MoOCl₄—n-Bu₄Sn—EtOH (mole ratio 1:1:1) as catalyst. Phenylacetylenes with no or sterically small ortho-substituents did not polymerize in a living fashion. On the other hand, in the polymerization of phenylacetylenes having medium-sized substituents (e.g., CH₃, Cl, Br, and iPr), the number-average molecular weights M_n of polymers increased in direct proportion to monomer consumption, while the polydispersity ratios were 1,2– 1,3, which is in favor of living polymerization. Further, monomers having bulky ortho-groups (CF₃ and Me₃Ge) exhibited excellent living nature with small polydispersity ratios of ≈ 1,1. Thus, it is concluded that not the electronic but the steric effect of the ortho-substituent is important to achieve living polymerization.     

Inhibition of MAP kinase activity moderates changes in expression and function of Cx32 but not claudin-1 during DNA synthesis in primary cultures of rat hepatocytes

The signal transduction pathways and activation of the MAP kinase or PI3 kinase signaling cascade regulate a variety of cellular processes, including proliferation and differentiation in hepatocytes. To elucidate the mechanisms of signal transmission required for the regulation of gap and tight junctions during DNA synthesis in rat hepatocytes, we determined changes of expression and function of gap and tight junctions of cells grown in primary culture, using inhibitors of signaling pathways for MAP kinase (PD98059) and PI3 kinase (LY294002). During the stimulation of DNA synthesis induced by epidermal growth factor (EGF), immunoreactivity and mRNAs of gap junction protein Cx32 and of tight junction protein claudin-1 markedly decreased with reduction of gap junctional intercellular communication (GJIC) and the fence function of tight junctions. In Western blots, whole-cell lysate of claudin-1 protein decreased and phosphorylated Cx32 protein in the insoluble fraction of Triton X-100 increased during the stimulation of DNA synthesis. During reinhibition of DNA synthesis, the changes of Cx32 and claudin-1 returned to control levels, as did both functions. In treatment with the inhibitors before DNA synthesis, PD98059 inhibited the changes of expression and function of Cx32, but not claudin-1, without inhibition of cell growth, whereas LY294002 completely inhibited cell growth. These findings indicate that the PI3 kinase pathway rather than the MAP kinase pathway plays an important role for EGF-induced proliferation of rat hepatocytes, and that changes of Cx32 in hepatocytes during the stimulation of DNA synthesis may be in part controlled through MAP kinase. Furthermore, Cx32, but not claudin-1, protein may be a target of activated MAP kinase in hepatocytes.