Indane-1,3-diones IX, synthèse et activité anti-inflammatoire de 2-polyaza-arylindane-1,3-diones et de leurs dérivés N- ou O-substitués

Les auteurs étudient les voies d'accès à des 2-polyaza-arylindane-1,3-diones et à leurs dérivés diversement substitués sur l'hétérocycle et l'homocycle ainsi que la pharmacomodulation de leur activité anti-inflammatoire. Ces β dicétoénamines fournissent en milieu alcalin des anions multidents conduisant en présence d'agents électrophiles à une C, N ou O-substitution; la mise en œuvre de la réaction de Mitsunobu a abouti à une N-(ω-amino-)-alkylation régiospécifique ou régiosélective. Parmi les diverses modifications structurales, la N-éthylation de la molécule de base, éventuellement couplée avec une méthoxylation en 5 sur l'homocycle s'est avérée efficace pour l'émergence d'une activité anti-inflammatoire en séries pyridazinyle, pyrimidinyle et tétrazolyle. Parmi les 3 molécules les plus actives 31, 43 et 50, la seconde a fait l'object d'une étude plus approfondie.     

银耳多糖对小鼠脾细胞内游离钙离子浓度的影响

为进一步探讨银耳多糖(TP)免疫调节作用的机制,建立了特异性荧光探针Fura-2测定脾细胞内游离钙离子浓度的方法,观察TP对脾细胞内游离钙离子浓度的影响。结果表明,TP在一定剂量范围内可以剂量依赖方式增加脾细胞内游离钙离子的浓度,并与ConA有协同作用。在外钙为零时,TP对内钙释放无影响,钙通道阻断剂维拉帕米(verapamil 10μg·mL^-1)可阻断TP升高脾细胞内游离钙离子浓度的作用。     

Vascularisation of the head of the radius in the adult

Summary Although rare, ischemic necrosis of the head of the radius after fracture is a theoretic possibility. The epiphyseal vascularisation of the proximal end of the radius was studied by dissection and diaphanisation techniques. The main extra-osseous supply is derived from epiphyseo-metaphyseal arteries given off by the recurrent radial a. and the first collateral of the ulnar a. These, to the number of three or four, anastomose together in a peri-cervical arterial circle continuous with the periosteal vessels of the shaft. From the proximal part of this network there arise three main intra-epiphyseal branches, which traverse the head, but nearly the entire periphery of the osteochondral junction is the site of small periosteal branches penetrating the head, though to no great depth. When the head of the radius is fractured, the commonest displacement is posterolateral, and the main vessel-bearing periosteal layer probably remains intact.

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Contribution à l'étude de la vascularisation de la tête du radius de l'adulte

Résumé Bien qu'exceptionnelle, la nécrose ischémique post-fracturaire de la tête radiale reste théoriquement possible. La vascularisation épiphysaire de la partie proximale du radius a été étudiée par des techniques de dissection et de diaphanisation. L'apport extraosseux principal provient d'artères épiphyso-métaphysaires issues de l'a. récurrente radiale et de la première a. collatérale de l'a. ulnaire. Celles-ci, au nombre de trois ou quatre, s'anastomosent en un cercle artériel péricervical en continuité avec la vascularisation périostée diaphysaire. De la partie postérolatéral de ce réseau naissent trois branches intra-épiphysaires principales, traversant la tête, mais presque toute la périphérie de la jonction ostéochondrale est le siège de petites branches périostées pénétrant la tête sur une faible profondeur. Lors d'une fracture de la tête radiale, le déplacement postéro-latéral le plus fréquent, respecte probablement la lame périostée porte-vaisseaux principale.

     

苄普地尔与山莨菪碱合用对心肌缺血再灌注损伤的保护作用

卡普地尔与山莨菪碱合用对结扎大鼠冠脉左室支造成心肌缺血再灌注损伤的保护作用。两药同时合用可降低缺血再灌性心律失常发生率;明显提高复灌后心肌超氧物歧化酶活性及显著减轻心肌超微结构损伤。表明两药合用有协同作用,较单用苄普地尔或山莨菪碱疗效好。     

The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming (alpha) subunits of voltage-gated Na+ (Na(v)) channels. The neurological phenotypes seen in Fgf14-/- mice and the identification of an FGF14 missense mutation (FGF14(F145S)) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14(F145S) reduces Na(v) alpha subunit expression at the axon initial segment, attenuates Na(v) channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14(F145S) does not interact directly with Na(v) channel alpha subunits. Rather, FGF14(F145S) associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Na(v) alpha subunits, suggesting that the mutant FGF14(F145S) protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Na(v) channel alpha subunits and altering neuronal excitability.     

Human papillomavirus infection: Epidemiology,biology, host interactions,cancer development,prevention, and therapeutics

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. It is caused by the HPV, a DNA virus that infects epithelial cells in various mucous membranes and skin surfaces. HPV can be categorised into high-risk and low-risk types based on their association with the development of certain cancers. High-risk HPV types, such as HPV-16 and HPV-18, are known to be oncogenic and are strongly associated with the development of cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These types of HPV can persist in the body for an extended period and, in some cases, lead to the formation of precancerous lesions that may progress to cancer if left untreated. Low-risk HPV types, such as HPV-6 and HPV-11, are not typically associated with cancer but can cause benign conditions like genital warts. Genital warts are characterised by the growth of small, cauliflower-like bumps on the genital and anal areas. Although not life-threatening, they can cause discomfort and psychological distress. HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can also be transmitted through non-penetrative sexual activities that involve skin-to-skin contact. In addition to sexual transmission, vertical transmission from mother to child during childbirth is possible but relatively rare. Prevention of HPV infection includes vaccination and safe sexual practices. HPV vaccines, such as Gardasil and Cervarix, are highly effective in preventing infection with the most common high-risk HPV types. These vaccines are typically administered to adolescents and young adults before they become sexually active. Safe sexual practices, such as consistent and correct condom use and limiting the number of sexual partners, can also reduce the risk of HPV transmission. Diagnosis of HPV infection can be challenging because the infection is often asymptomatic, especially in men. In women, HPV testing can be done through cervical screening programs, which involve the collection of cervical cells for analysis. Abnormal results may lead to further diagnostic procedures, such as colposcopy or biopsy, to detect precancerous or cancerous changes. Overall, HPV infection is a prevalent sexually transmitted infection with significant implications for public health. Vaccination, regular screening, and early treatment of precancerous lesions are key strategies to reduce the burden of HPV-related diseases and their associated complications. Education and awareness about HPV and its prevention are crucial in promoting optimal sexual health. This study aimed to carry out a literature review considering several aspects involving HPV infection: Global distribution, prevalence, biology, host interactions, cancer development, prevention, therapeutics, coinfection with other viruses, coinfection with bacteria, association with head and neck squamous cell carcinomas, and association with anal cancer.     

纳米羟基磷灰石沉积层/钛酸钾薄层/钛合金生物复合材料体外培养成骨细胞的研究

在制备出具有表面活性的纳米羟基磷灰石沉积层/钛酸钾薄层/钛合金（HA/K2Ti6O13/β-Ti）生物复合材料的基础上,将体外培养的成骨细胞与HA/K2Ti6O13/β-Ti生物复合材料、未经处理β钛合金两种骨替代材料共同培养,在既定时间内观察两种骨替代材料对成骨细胞生长、附着的影响。结果表明两种骨替代材料对成骨细胞生长无明显抑制或促进作用,均具有良好的细胞相容性,它们皆能使成骨细胞附着于各自材料表面,分泌形成胶原纤维样基质。HA/K2Ti6O13/β-Ti生物复合材料较β钛合金具有更优异的的生物活性和成骨性能,是一种很好的生物植入材料。     

Comparison Between Living Donor Liver Transplantation Recipients Who Met the Milan and UCSF Criteria After Successful Downstaging Therapies

Background and Aims

Various downstaging therapies were introduced to liver recipients who could not meet the relative criteria for liver transplantation, and many endpoints were reported. The most common criteria used were the Milan criteria and the University of California, San Francisco (UCSF) criteria. However, no comparison was made between them, and we attempted to find possible differences between the living donor liver transplantation (LDLT) patients who met the Milan criteria and those who met the UCSF criteria after accepting preoperative downstaging therapies.

Materials and Methods

We performed a retrospective study of all 72 patients at our center from January 2003 to March 2009 who were diagnosed with advanced hepatocellular carcinoma but accepted various downstaging therapies. Some patients met the Milan criteria (group 1), and some met the UCSF criteria (group 2) but not the Milan criteria. We collected the data from the two groups and then compared the preoperative demographic data, downstaging therapies, intraoperative data from LDLT, and the recovery and complications after LDLT. Survival rates were compared using Kaplan?CMeier analysis.

Results

Only 44 patients (61.1?%) met the criteria for liver transplantation, 21 cases met the Milan criteria (group 1), and 23 cases met the UCSF criteria (group 2) but not the Milan criteria. All of the 44 patients accepted right lobe living liver donor liver transplantation in our center. The difference in the baseline characteristics between the two groups did not reach statistical significance. The mean number of downstaging treatments per patient was 1.81?±?0.35 in group 1 and 1.83?±?0.41 in group 2 (P?=?0.928). Most of the patients received only one downstaging treatment, and transcatheter arterial chemoembolization (TACE) was the most common downstaging therapy. Four patients suffered complications after downstaging therapies: intra-abdominal hemorrhage after right hepatectomy, upper gastrointestinal hemorrhage after TACE, biliary fistula after resection, and hand?Cfoot syndrome after taking sorafenib. All complications after LDLT, classified according to the Clavien?CDindo system, were compared within the two groups, and the calculated score of the complications in group 1 was 1.48?±?1.63, which was greater than that of group 2 (1.39?±?1.64), but this difference did not reach statistical significance (P?=?0.865). The 1-, 3-, and 5-year survival rates were 90.4, 76.2, and 71.4?% in group 1 and 91.3, 73.9, and 69.6?% in group 2, respectively (P?>?0.05). Seven patients (three in group 1 and four in group 2) had tumor recurrence after a median follow-up period of 72?months. The pathology findings were not different between the two groups.

Conclusion

Recipients who meet the Milan or UCSF criteria after accepting successful preoperative downstaging therapy in LDLT can achieve the same result.     

Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: A double-blind placebo-controlled trial

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients’ feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.