元胡止痛胶囊的含药血清对痛经模型动物的影响

目的采用血清药理学实验方法 ,观察元胡止痛胶囊的含药血清对痛经模型动物的影响。方法缩宫素诱发大鼠痛经模型和前列腺素E诱发小鼠痛经模型法,对大鼠离体子宫收缩活动的影响。结果元胡止痛胶囊的含药血清能减少缩宫素所致大鼠扭体反应次数和前列腺素E1所致小鼠扭体反应次数,并能拮抗缩宫素对大鼠离体子宫的收缩作用。结论元胡止痛胶囊的含药血清对痛经模型动物有镇痛作用,并对大鼠离体子宫收缩有解痉作用。     

Prevalence and predictors of dysmenorrhea among a population of adolescent’s schoolgirls (Morocco)

Dysmenorrhea is the most common gynaecological problem among young females. In Arabic countries, few studies on gynaecological problems of adolescent’s girls were published. Objective: the aim of the study was to determine the prevalence of dysmenorrhea and associated factors among adolescents in public schools at Marrakesh. Methods: we conducted a cross-sectional study; our data was collected via a questionnaire and the statistical analysis was done using SPSS version 21. Our random sample counted 364 post-menarcheal girls aged between 12 and 20 years who participated voluntarily in our study. Results: the mean age at menarche was 12.89 ± 1.34 years; the prevalence of dysmenorrhea was 78% and 58.1% of them suffering from severe dysmenorrhea that increased clearly with the chronological age. Dysmenorrhea was cause for missing school among 13% of girls and the most common symptoms associated with it were backache, fatigue, irritability and anxiety. The gynecological age was found to be the only predictive factor of dysmenorrhea among schoolgirls. Conclusion: reproductive health education should be improved enough by including them in the school curriculum to prepare girls for menstruation and inform them about problems related to this phenomenon, especially dysmenorrhea.     

Biofeedback-assisted relaxation training for primary dysmenorrhea: A case study

Primary dysmenorrhea is a familiar complaint to medical practitioners. Recently, behavior therapy has been shown to be an effective treatment for the symptoms of dysmenorrhea. The present case study offers biofeedback-assisted relaxation treatment as an effective alternative treatment. The Menstrual Symptom Questionnaire was used to classify dysmenorrhea as spasmodic or congestive. This classification provides homogeneous groups of patients. The patient in this study had an 18-year history of primary dysmenorrhea that was resistant to hormonal and analgesic treatment. After two months of baseline observation, she was given eight sessions of skin-temperature biofeedback and autogenic training. She reported significant reduction of pain and discomfort with the use of biofeedback-assisted relaxation. Desensitization using visual imagery, an important component of previous therapies, was not used. Further examination of the efficacy of biofeedback-assisted relaxation training for the treatment of both congestive and spasmodic dysmenorrhea is suggested.     

CURRENT CONCEPTS OF PRIMARY DYSMENORRHEA

Menstruation, a physiologic function, should be free of organic or psychic discomfort, but often it is not.As to somatic causes, much has been postulated, little proved. There is evidence that somatic dysmenorrhea is caused by action of progesterone upon the uterus. And there is indication also that the cause may lie in some abnormality of the cervix or abnormal effect upon it.Traditional association of menstruation with “illness,” “curse” and the like is indicative of the psychic roots of dysmenorrhea. It has been observed that there is striking parallel between dysmenorrhea in adulthood and psychological maladjustment in childhood. Cure of psychogenic dysmenorrhea may be difficult. Proper anticipation—emotional preparation of the girl from infancy on, then sound instruction in biologic fact—would seem to be a major means of prevention.     

Biofeedback-assisted relaxation training for primary dysmenorrhea: a case study.

Primary dysmenorrhea is a familiar complaint to medical practitioners. Recently, behavior therapy has been shown to be an effective treatment for the symptoms of dysmenorrhea. The present case study offers biofeedback-assisted relaxation treatment as an effective alternative treatment. The Menstrual Symptom Questionnaire was used to classify dysmenorrhea as spasmodic or congestive. This classification provides homogeneous groups of patients. The patient in this study had an 18-year history of primary dysmenorrhea that was resistant to hormonal and analgesic treatment. After two months of baseline observation, she was given eight sessions of skin-temperature biofeedback and autogenic training. She reported significant reduction of pain and discomfort with the use of biofeedback-assisted relaxation. Desensitization using visual imagery, an important component of previous therapies, was not used. Further examination of the efficacy of biofeedback-assisted relaxation training for the treatment of both congestive and spasmodic dysmenorrhea is suggested.     

Comparison between naproxen tablets and suppositories in primary dysmenorrhea

Naproxen tablets and suppositories were compared, in the treatment of primary dysmenorrhea, in a double-blind cross-over trial. The results on 32 patients treated during 128 menstruations with either tablets and suppositories were analysed. Both naproxen tablets and suppositories produced a significant but similar overall relief of dysmenorrhea, although the tablets had a better effect in relieving spasmodic pain than the suppositories (p < 0.05). Occasions of failure to obtain relief were not related to the occurrence of vomiting or diarrhea during the trial. Vomiting seems not to be responsible for the therapeutic failures of oral treatments with prostaglandin-synthetase inhibitors in primary dysmenorrhea.     

Paeonol alleviates primary dysmenorrhea in mice via activating CB2R in the uterus

Background and purposePrimary dysmenorrhea is the most common gynaecologic problem in menstruating women and is characterized by spasmodic uterine contraction and pain symptoms associated with inflammatory disturbances. Paeonol is an active phytochemical component that has shown anti-inflammatory and analgesic effects in several animal models. The aim of this study was to explore whether paeonol is effective against dysmenorrhea and to investigate the potential mechanism of cannabinoid receptor signalling.Experimental approachDysmenorrhea was established by injecting oestradiol benzoate into female mice. The effects of paeonol on writhing time and latency, uterine pathology and inflammatory mediators were explored. Isolated uterine smooth muscle was used to evaluate the direct effect of paeonol on uterine contraction.Key resultsThe oral administration of paeonol reduced dysmenorrhea pain and PGE2 and TNF-α expression in the uterine tissues of mice, and paeonol was found to be distributed in lesions of the uterus. Paeonol almost completely inhibited oxytocin-, high potassium- and Ca²⁺-induced contractions in isolated uteri. Antagonists of CB2R (AM630) and the MAPK pathway (U0126), but not of CB1R (AM251), reversed the inhibitory effect of paeonol on uterine contraction. Paeonol significantly blocked L-type Ca²⁺ channels and calcium influx in uterine smooth muscle cells via CB2R. Molecular docking results showed that paeonol fits well with the binding site of CB2R.Conclusions and implicationsPaeonol partially acts through CB2R to restrain calcium influx and uterine contraction to alleviate dysmenorrhea in mice. These results suggest that paeonol has therapeutic potential for the treatment of dysmenorrhea.     

Prostaglandin levels in endometrial jet wash specimens in patients with dysmenorrhea before and after indomethacin therapy.

A patient with functional primary dysmenorrhea of over two years duration was subjected to the endometrial jet wash technique during the period of active menstrual flow. Prostaglandin F analysis of the jet washings revealed significantly elevated levels during menstruation over normal control levels. Following indomethacin therapy, jet wash prostaglandin F levels were dramatically reduced and the patient became asymptomatic. A cause and effect relationsship between prostaglandin F and dysmenorrhea is suggested by these studied.     

Prostaglandin levels in endometrial jet wash specimens in patients with dysmenorrhea before and after indomethacin therapy

A patient with functional primary dysmenorrhea of over two years duration was subjected to the endometrial jet wash technique during the period of active menstrual flow. Prostaglandin F analysis of the jet washings revealed significantly elevated levels during menstruation over normal control levels. Following indomethacin therapy, jet wash prostaglandin F levels were dramatically reduced and the patient became asymptomatic. A cause and effect relationship between prostaglandin F and dysmenorrhea is suggested by these studies     

气滞痛经汤联合散结镇痛胶囊治疗原发性痛经应用效果及安全性

摘要 目的：探讨气滞痛经汤联合散结镇痛胶囊治疗原发性痛经应用效果及安全性。方法：选取我院2018年1月到2020年1月共收治的80例原发性痛经患者,按照随机数字法将所有患者均分为对照组（40例）和观察组（40例）。针对于不同组别患者应用不同的治疗方法,其中对照组应用散结镇痛胶囊口服治疗,观察组应用气滞痛经汤联合散结镇痛胶囊口服治疗,对比两组的治疗效果、治疗前后盆腔血流搏动指数(pulsatility index,PI)和阻抗指数(resistive index,RI)、治疗前后的疼痛持续时间、痛经评分、视觉模拟评分（visual analogue scale,VAS）以及不良反应发生率。结果：观察组的治疗总有效率为95.0 %,对照组的治疗总有效率为77.5 %,观察组明显高于对照组（P＜0.05）;两组治疗前左侧PI、右侧PI、左侧RI和右侧RI指标水平对比无明显差异（P＞0.05）,两组治疗后左侧PI、右侧PI、左侧RI和右侧RI指标水平对比差异显著,观察组明显低于对照组（P＜0.05）;两组治疗前疼痛持续时间、痛经评分和VAS评分对比无显著差异（P＞0.05）,两组治疗后三项疼痛指标评分较治疗前显著降低,且观察组低于对照组（P＜0.05）;比较两组的不良反应发生率,观察组（10.0 %）略高于对照组（5.0 %）,对比无显著差异（P＞0.05）。结论：对原发性痛经患者应用气滞痛经汤联合散结镇痛胶囊治疗,能够减轻患者的临床症状,降低双侧子宫脉血流动力学变化,降低患者的痛经程度,安全性好,值得临床应用推广。     

The early revascularization of membranous bone

The experimental finding that membranous onlay bone grafts maintain volume and viability to a greater extent than do endochondral grafts may be related to the more rapid vascularization of membranous bone. Microangiographic techniques were used to study the rates of vascularization of membranous and endochondral bone grafts in adult white New Zealand rabbits at 1, 3, 7, 14, and 21 days after bone grafting. Vascularization patterns were quantified microscopically using a modified point-counting technique. At 3 days, membranous bone grafts demonstrated vessel ingrowth from both soft tissue and host bone. Little ingrowth was seen in endochondral grafts. By day 7, 2.5 vessels per square were identified entering membranous grafts, while an average of 0.6 vessels per square were counted for endochondral bone grafts. At day 14, there was an average of greater than 20 vessels per square for membranous grafts versus 1.8 for their endochondral counterparts. At 21 days, the endochondral grafts demonstrated persistent avascular central areas not seen in membranous grafts. Membranous onlay bone grafts in the rabbit are more rapidly vascularized than endochondral grafts. This factor may affect the greater volume maintenance seen in experimental membranous grafts.     

Physical state of cytochrome oxidase: Relationship between membrane formation and ionic strength

Preparations of lipid-containing and lipid-depleted cytochrome oxidase from beef heart mitochondria through use of Triton non-ionic detergents is described. The lipid-containing oxidase is shown to form either a membranous or dispersed state. The dispersed state requires the presence of salt whereas the membranous condition is obtained by reducing the ionic strength. The membranous form shows low activity in comparison to the dispersed form. Typical unit membrane structure can be shown in sections of the membranous oxidase or in reaggregated membranous oxidase even though the lipid content is as low as eight percent. Both the dispersed and membranous oxidase show 50-Å globules by negative staining whereas the lipid-free oxidase shows strings of 20 Å diameter.     

The movement of membranous organelles in axons. Electron microscopic identification of anterogradely and retrogradely transported organelles

To identify the structures to be rapidly transported through the axons, we developed a new method to permit local cooling of mouse saphenous nerves in situ without exposing them. By this method, both anterograde and retrograde transport were successfully interrupted, while the structural integrity of the nerves was well preserved. Using radioactive tracers, anterogradely transported proteins were shown to accumulate just proximal to the cooled site, and retrogradely transported proteins just distal to the cooled site. Where the anterogradely transported proteins accumulated, the vesiculotubular membranous structures increased in amount inside both myelinated and unmyelinated axons. Such accumulated membranous structures showed a relatively uniform diameter of 50--80 nm, and some of them seemed to be continuous with the axonal smooth endoplasmic reticulum (SER). Thick sections of nerves selectively stained for the axonal membranous structures revealed that the network of the axonal SER was also packed inside axons proximal to the cooled site. In contrast, large membranous bodies of varying sizes accumulated inside axons just distal to the cooled site, where the retrogradely transported proteins accumulated. These bodies were composed mainly of multivesicular bodies and lamellated membranous structures. When horseradish peroxidase was administered in the distal end of the nerve, membranous bodies showing this activity accumulated, together with unstained membranous bodies. Hence, we are led to propose that, besides mitochondria, the membranous components in the axon can be classified into two systems from the viewpoint of axonal transport: "axonal SER and vesiculotubular structures" in the anterograde direction and "large membranous bodies" in the retrograde direction.     

The refief of primary dysmenorrhea by ketoprofen and indomethacin

The prostaglandin biosynthesis inhibitors ketoprofen and indomethacin were compared in the treatment of primary dysmenorrhea in a double-blind, cross-over trial involving 23 patients. Each drug was used for 2-4 days during 3 consecutive menstruations in randomized order. Good or moderate overall relief was obtained in 60 of the 68 ketoprofen-treated menstruations (88%). A dysmenorrhea score, based on subjective estimations of 8 symptoms, similarly decreased from a mean (+/- S.E.M.) basal level of 9.6 +/- 0.6 to 3.6 +/- 0.3 during ketoprofen treatment and to 4.0 +/- 0.3 during indomethacin. Both drugs relieved pelvic and lower back pains and eliminated vomiting and diarrhea in 82-97% of the cycles whereas headache, fatigue and nervousness were less frequently alleviated (40-67%). Eighteen of the 23 women (78%) had been unable to work during the first day of menstruation, the rate of working days lost was reduced to 4% with ketoprofen and 9 with indomethacin. Mild side-effects occurred during 12 ketoprofen and 14 indomethacin therapies. Ketoprofen thus seems to be as effective and tolerable as indomethacin in the treatment of primary dysmenorrhea.     

Isolation and reconstitution of the membrane-bound form of dopamine beta-hydroxylase

Dopamine beta-hydroxylase is present in the bovine adrenal medulla in two forms, soluble and membrane bound. Previous isolation procedures for the membranous hydroxylase have resulted in a form of enzyme identical in subunit structure with the soluble type. We report here the isolation of a membrane-bound form of dopamine beta-hydroxylase which is structurally different from the soluble form. The isolated membranous enzyme has a large apparent molecular weight on gel filtration, is amphiphilic, and contains bound phospholipid which is predominantly phosphatidylserine. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate shows that the membranous hydroxylase contains two nonidentical subunits under both reducing and nonreducing conditions. Under reducing conditions the apparent molecular weights of the two subunits are 70,000 and 75,000 and both contain carbohydrate. The purified membranous hydroxylase binds to phospholipid vesicles and chymotryptic digestion of the bound enzyme suggests that two forms of the membranous hydroxylase exist.     

Bioactive constituents and the molecular mechanism of Curcumae Rhizoma in the treatment of primary dysmenorrhea based on network pharmacology and molecular docking

BackgroundCurcumae Rhizoma (CR) has a clinical efficacy in activating blood circulation to dissipate blood stasis and has been used for the clinical treatment of qi stagnation and blood stasis (QSBS) primary dysmenorrhea for many years. However, its molecular mechanism is unknown.ObjectiveThe present study aimed to demonstrate the multicomponent, multitarget and multipathway regulatory molecular mechanisms of CR in the treatment of QSBS primary dysmenorrhea.MethodsObservations of pathological changes in uterine tissues and biochemical assays were used to confirm that a rat model was successfully established and that CR was effective in the treatment of QSBS primary dysmenorrhea. The main active components of CR in rat plasma were identified and screened by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The component-target-disease network and protein-protein interaction (PPI) network of CR were constructed by a network pharmacology approach. Then, we performed Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was adopted to verify the interactions between the core components and targets of CR to confirm the accuracy of the network pharmacology prediction results. Furthermore, we evaluated the bioactive constituents of CR and molecular mechanism of by which CR promote blood circulation and remove blood stasis via platelet tests in vivo and in vitro and Western blot analysis.ResultsThe results of HE staining and biochemical assays of PGF2α, TXB2 and Ca²⁺ showed that CR was effective in the treatment of QSBS primary dysmenorrhea. A total of 36 active components were identified in CR, and 329 common targets were obtained and used to construct the networks. Of these, 14 core components and 10 core targets of CR in the treatment of primary dysmenorrhea were identified. The GO and KEGG enrichment analyses revealed that the common targets were involved in multiple signaling pathways, including the calcium, cAMP, MAPK, and PI3K-Akt signaling pathways, as well as platelet activation, which is closely related to platelet aggregation. The molecular docking results showed that the 14 core components and 10 core targets could bind spontaneously. Two core targets (MAPK1 and CCR5) and 7 core components (Isoprocurcumenol, Curcumadione, Epiprocurcumenol, (+)-Curdione, Neocurdione, Procurcumenol, and 13-Hydroxygermacrone) were closely related to CR in the treatment of primary dysmenorrhea. Furthermore, the in vivo platelet test showed that CR clearly inhibited platelet aggregation. Five core components ((+)-Curdione, Neocurdione, Isoprocurcumenol, Curcumadione and Procurcumenol) obviously inhibited platelet aggregation in vitro. In addition, based on the relationships among the signaling pathways, we confirmed that CR can effectively inhibit the expression of MAPK and PI3K-Akt signaling pathway-related proteins and decrease the protein expression levels of ERK, JNK, MAPK, PI3K, AKT and CCR5, thereby inhibiting platelet aggregation.ConclusionThis study demonstrated the bioactive constituents and mechanisms of CR in promoting blood circulation and removing blood stasis and its multicomponent, multitarget and multipathway treatment characteristics in primary dysmenorrhea. The results provide theoretical evidence for the development and utilization of CR.     

Hepatitis C Virus-Induced Cytoplasmic Organelles Use the Nuclear Transport Machinery to Establish an Environment Conducive to Virus Replication

Hepatitis C virus (HCV) infection induces formation of a membranous web structure in the host cell cytoplasm where the viral genome replicates and virions assemble. The membranous web is thought to concentrate viral components and hide viral RNA from pattern recognition receptors. We have uncovered a role for nuclear pore complex proteins (Nups) and nuclear transport factors (NTFs) in the membranous web. We show that HCV infection leads to increased levels of cytoplasmic Nups that accumulate at sites enriched for HCV proteins. Moreover, we detected interactions between specific HCV proteins and both Nups and NTFs. We hypothesize that cytoplasmically positioned Nups facilitate formation of the membranous web and contribute to the compartmentalization of viral replication. Accordingly, we show that transport cargo proteins normally targeted to the nucleus are capable of entering regions of the membranous web, and that depletion of specific Nups or Kaps inhibits HCV replication and assembly.     

Evaluation of nitric oxide and homocysteine levels in primary dysmenorrheal women in Taiwan

In this study, we investigated the possible pathophysiological mechanisms in primary dysmenorrhea. The study was undertaken to determine the effect of homocysteine on the nitric oxide (NO) pathway in primary dysmenorrheal women. A total of 94 students from a local nursing college participated. Group 1 consisted of 51 normal subjects with no dysmenorrhea. Group 2 had 43 subjects with dysmenorrheal symptoms. Our results show that serum NO levels in group 2 are higher than those in group 1. However, the serum homocysteine level was lower in group 2. These observations indicate that the NO pathway is involved in the pathophysiological mechanism responsible for the damaging effects of homocysteine on dysmenorrheal women.     

The relief of primary dysmenorrhea by ketoprofen and indomethacin

The prostaglandin biosynthesis inhibitors ketoprofen and indomethacin were compared in the treatment of primary dysmenorrhea in a double-blind, cross-over trial involving 23 patients. Each drug was used for 2–4 days during 3 consecutive menstruations in randomized order. Good or moderate overall relief was obtained in 60 of the 68 ketoprofen-treated menstruations (88 %) and in 60 of the indomethacin-treated cases (90 %). A dysmenorrhea score, based on subjective estimations of 8 symptoms, similarly decreased from a mean (±S.E.M.) basal level of 9.6 ± 0.6 to 3.6 ± 0.3 during ketoprofen treatment and to 4.0 ± 0.3 during indomethacin. Both drugs relieved pelvic and lower back pains and eliminated vomiting and diarrhea in 82–97 % of the cycles whereas headache, fatigue and nervousness were less frequently alleviated (40–67 %). Eighteen of the 23 women (78 %) had been unable to work during the first day of menstruation, the rate of working days lost was reduced to 4 % with ketoprofen and 9 with indomethacin. Mild side-effects occurred during 12 ketoprofen and 14 indomethacin therapies. Ketoprofen thus seems to be as effective and tolerable as indomethacin in the treatment of primary dysmenorrhea.     

Differential turnover of axonally transported glycoproteins

Metabolic turnover of axonally transported glycoproteins has been examined in membranous and soluble subfractions of goldfish optic tectum following intraocular injection of [³H]fucose. Radioactivity in total transported glycoproteins reached a maximum in the tectum after 24–30 hr, then declined with a half-life of approximately 20 days. Radioactivity in the total membranous subfraction declined with a similar half-life of 20–21 days while radioactivity in the soluble fraction showed a significantly shorter half-life of approximately seven days. Various sized glycopeptides derived from the membranous subfraction showed differential rates of loss of radioactivity with the lower molecular weight nondialyzable molecules displaying the most rapid turnover. In contrast, the glycopeptides derived from the soluble fraction showed relatively uniform rates of turnover. The results are discussed in the context of metabolic compartmentalization between membranous and soluble glycoproteins and among the carbohydrate chains of the membranous molecules.Supported by NIH grant NS 11456.