A Familial Case of Multiple Endocrine Neoplasia 2A: From Morphology to Genetic Alterations Penetration in Three Generations of a Family.

This paper illustrates a rare syndrome of multiple endocrine neoplasia type 2A (MEN2A) in a family of three generations. In our case, the father, son and one daughter developed phaeochromocytoma (PHEO) and medullary thyroid carcinoma (MTC) over a period of 35 years. Because of the metachronous onset of the disease and lack of digital medical records in the past, the syndrome was not found until a recent fine needle aspiration of an MTC-metastasized lymph node from the son. All resected tumors from the family members were then reviewed and supplemented with immunohistochemical studies, previously wrong diagnoses were then corrected. Further molecular study of targeted sequencing also revealed a RET germline mutation (C634G) in the family tree including the three members with onset of the disease and one granddaughter who had no disease at the time of testing. Despite the syndrome being well-known, it may still be misdiagnosed because of its rarity and long disease onset. A few lessons can be learned from this unique case. Successful diagnosis requires high suspicion and surveillance and a tri-level methodology including a careful review of family history, pathology and genetic counselling.

The Effect of immunotherapy on oligometastatic non-small cell lung cancer patients by sites of metastasis.

Introduction: The efficacy of immunotherapy for treatment of patients with oligometastatic non-small cell lung cancer (NSCLC) at different metastatic sites remains controversial. We investigated the effect of different metastatic sites on immunotherapy for oligometastatic NSCLC following local treatment (LT). Methods: We retrospectively analyzed patients with oligometastatic NSCLC from the latest 2018 registry on the SEER Stat software (8.3.9. Version) and a Chinese single-center cohort. The effects of immunotherapy on OS (overall survival) and CSS (cancer specific survival) were estimated for patients with different metastatic sites. Results: A total of 483 patients in the SEER-18 database and 344 patients in the single-center cohort were included. Immunotherapy was significantly correlated with improved OS (SEER: Hazard ratio 0.754, 95% CI 0.609-0.932; P=0.044; China: Hazard ratio 0.697, 95% CI 0.542-0.896; P=0.005) and CSS (SEER: Hazard ratio 0.743, 95% CI 0.596-0.928; P=0.009; China: Hazard ratio 0.725, 95% CI 0.556-0.945; P=0.018). Subgroup analysis showed that OS was improved after immunotherapy in the BRM (SEER: Hazard ratio 0.565, 95% CI 0.385-0.829; P=0.004; China: Hazard ratio 0.536, 95% CI 0.312-0.920; P=0.024) and MOM (SEER: Hazard ratio 0.524, 95% CI 0.290-0.947; P=0.032; China: Hazard ratio 0.469, 95% CI 0.235-0.937; P=0.032) subgroups, but not in the BOM (SEER: P=0.334; China: P=0.441), LIM (SEER: P=0.301; China: P=0.357), or OTM (SEER: P=0.868; China: P=0.489) subgroups. Conclusions: This study showed that immunotherapy conferred survival benefits on patients with oligometastatic NSCLC. Our subgroup analysis suggested that patients with oligometastatic NSCLC in the brain or multiple organs may particularly benefit from aggressive front-line therapies.

[Time-dependent injury of mouse cerebral cortex and hippocampus by acute hypoxia].

The aim of this study was to investigate the harmful effects of acute hypoxia on mouse cerebral cortex and hippocampus and the underlying mechanism. Mouse model of acute hypoxia was constructed by using a sealed glass jar. Laser speckle contrast imaging was used to detect the changes of cerebral blood flow after different time duration of hypoxia. Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) assay kits were used to detect oxidative stress in cerebral cortex and hippocampus. Immunofluorescent staining was used to detect neuroinflammatory response of microglia in the cerebral cortex and hippocampus. One-step TUNEL method was used to detect neuronal apoptosis. The results showed that, compared with non-hypoxia (0 min hypoxia) group, 30 min hypoxia group exhibited decreased cerebral blood flow, higher percentage of CD68+/Iba1+ microglia, and increased neural apoptosis in the cerebral cortex and hippocampus. Compared with 30 min group, 60 min hypoxia group showed significantly decreased cerebral blood flow, increased MDA content in the cortex, as well as greater percentage of CD68+/Iba1+ microglia and neuronal apoptosis in the cerebral cortex and hippocampus. These results suggest that acute hypoxia damages brain tissue in a time-dependent manner and the oxidative stress and neuroinflammation are important mechanisms.

[Clinical results of arthroscopic anterior cruciate ligament reconstruction with short femoral tunnel].

OBJECTIVE: To evaluate the clinical outcome of arthroscopic reconstruction of anterior cruciate ligament (ACL) with short femoral tunnel. METHODS: From May 2013 to June 2017, 128 patients with anterior cruciate ligament reconstruction were performed with Transportal technique. Among them, 32 cases had short femoral tunnel were included, including 13 males and 19 females, aged 25.8 (17 to 43) years old, with a mean history of (4.5±1.1) months. The tibial tunnels were drilled in the middle of the footprint of the ACL, and femoral tunnels were drilled by transportal technique. Grafts were fixed with Endobutton at the femoral side and with interference screw at the tibial side. The changes of symptoms and signs were observed and the anterior tibial displacement was measured. The function of knee joint was evaluated by Lysholm score and Tegner score. RESULTS: All patients were followed up for over 2 years. At the latest follow-up, 30 patients were negative and 2 patients were positive in knee shift test; 28 patients were negative in Lachman sign, 4 patients were positive in degree I; 30 patients were negative in anterior drawer test, 1 patient was positive in degree I and 1 patient was positive in degree II. The anterior displacement of the tibia increased by (2.6±1.8) mm compared with the healthy side, which was significantly different from that before operation (t=19.77, P<0.05). Lysholm score of 82.2±6.1 was significantly higher than that before operation (t=17.33, P=0.001). According to Lysholm score evaluation, 15 cases got an excellent result, 10 were good, 7 were fair, and no bad results, with a significant difference compared with that before operation (z=-7.151, P<0.05). Tegner motor function score of (7.4±0.6) was significantly different from that before operation (t=9.11, P=0.000 5). After operation, the knee joint movement ability of the patients improved significantly. Twelve patients could participate in antagonistic sports and 15 patients could participate in non-antagonistic sports. Fifteen patients were very satisfied with the curative effect, 13 patients were satisfied with the curative effect. CONCLUSIONS: The incidence of short femoral tunnel in anterior cruciate ligament reconstruction with transportal technique is 25%. At present, the clinical effect of patients with short tunnel is acceptable. However, due to the lack of comparative study, the effect of short tunnel on the curative effect is still unclear.

[Acupuncture treatment of oligoasthenozoospermia].

Studies show that acupuncture can significantly elevate the level of serum testosterone (T), reduce the concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), initiate spermatogenesis, enhance testicular blood flow, maintain a relative low temperature in the testis, increase the concentration, motility and antioxidative injury capability of spermatozoa by raising the levels of seminal α-glucosidase, fructose and super oxide dismutase, and eventually improve semen quality and the rate of conception in the treatment of oligoasthenozoospermia. Currently, the quality of the clinical studies of acupuncture treatment of oligoasthenozoospermia is relatively poor, the existing evidence remains at a low level, its clinical application is limited, and its therapeutic effect has to be further verified. The present paper summarizes the literature from domestic and international databases about acupuncture treatment of oligoasthenozoospermia, and offers an overview of the effects of acupuncture on the reproductive endocrine system, testicular blood flow, semen quality, and rate of conception in the treatment of the patient.

[Research on glucose measuring technique by surface plasmon resonance based on thiol coupling].

In the glucose measuring technique by surface plasmon resonance, D-galactose/D-glucose binding protein (GGBP) that can specifically adsorb glucose was introduced, and high-precision specific detection of glucose concentration was realized. In the present paper, the GGBP protein was bound on the surface of SPR sensor through thiol coupling method. GGBP binding experiment was carried out on SPR sensor and then glucose concentration experiment was conducted with this sensor. The results indicated that the SPR sensor had good linearity, stability and repeatability in the range of 0.1-10 mg x dL(-1). SPR sensor bound with GGBP would have great potential and vast development prospects.

Concurrent involved-field radiotherapy and XELOX in gastric cancer patients with postoperative oligometastatic recurrence.

PURPOSE: The aim of this study was to retrospectively observe gastric adenocarcinoma patients with postoperative oligometastatic recurrence and investigated the effects of concurrent involved-field radiotherapy (RT) and XELOX on progression-free survival (PFS). PATIENTS AND METHODS: From 2008 to 2011, 246 patients underwent curative resection of gastric carcinoma was enrolled. A retrospective review was performed on 34 patients with distant recurrence. Among them, 19 patients were oligometastases patients, where 13 patients received involved-field RT with a dose of 40-60 Gy by an intensity-modulated RT technique and concurrent XELOX chemotherapy, four patients were treated with XELOX chemotherapy alone (oxaliplatin 130 mg/m2, capecitabine 1000 mg/m2, twice daily, 3 week each cycle), and two patients with only brain metastasis were not included in the analysis. RESULTS: The median PFS was 11 months in the 13 oligometastatic patients who received concurrent involved-field RT and XELOX. The oligometastatic patients receiving concurrent radiochemotherapy trended toward a better median PFS when compared with those receiving chemotherapy alone. CONCLUSIONS: For patients with postoperative oligometastatic recurrence, concurrent involved-field RT and XELOX showed better responses and was a choice for first-line treatment.

Genome Sequence of the Banana Pathogen Dickeya zeae Strain MS1, Which Causes Bacterial Soft Rot.

We report a draft genome sequence of Dickeya zeae strain MS1, which is the causative agent of banana soft rot in China, and we show several of its specific properties compared with those of other D. zeae strains. Genome sequencing provides a tool for understanding the genomic determination of the pathogenicity and phylogeny placement of this pathogen.

Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells.

The intestinal microbiota has a critical role in immune system and metabolic homeostasis, but it must be tolerated by the host to avoid inflammatory responses that can damage the epithelial barrier separating the host from the luminal contents. Breakdown of this regulation and the resulting inappropriate immune response to commensals are thought to lead to the development of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. We proposed that the intestinal immune system is instructed by the microbiota to limit responses to luminal antigens. Here we demonstrate in mice that, at steady state, the microbiota inhibits the transport of both commensal and pathogenic bacteria from the lumen to a key immune inductive site, the mesenteric lymph nodes (MLNs). However, in the absence of Myd88 or under conditions of antibiotic-induced dysbiosis, non-invasive bacteria were trafficked to the MLNs in a CCR7-dependent manner, and induced both T-cell responses and IgA production. Trafficking was carried out by CX(3)CR1(hi) mononuclear phagocytes, an intestinal-cell population previously reported to be non-migratory. These findings define a central role for commensals in regulating the migration to the MLNs of CX(3)CR1(hi) mononuclear phagocytes endowed with the ability to capture luminal bacteria, thereby compartmentalizing the intestinal immune response to avoid inflammation.

Relief of preintegration inhibition and characterization of additional blocks for HIV replication in primary mouse T cells.

Development of a small animal model to study HIV replication and pathogenesis has been hampered by the failure of the virus to replicate in non-primate cells. Most studies aimed at achieving replication in murine cells have been limited to fibroblast cell lines, but generating an appropriate model requires overcoming blocks to viral replication in primary T cells. We have studied HIV-1 replication in CD4(+) T cells from human CD4/CCR5/Cyclin T1 transgenic mice. Expression of hCD4 and hCCR5 in mouse CD4(+) T cells enabled efficient entry of R5 strain HIV-1. In mouse T cells, HIV-1 underwent reverse transcription and nuclear import as efficiently as in human T cells. In contrast, chromosomal integration of HIV-1 proviral DNA was inefficient in activated mouse T cells. This process was greatly enhanced by providing a secondary T cell receptor (TCR) signal after HIV-1 infection, especially between 12 to 24 h post infection. This effect was specific for primary mouse T cells. The pathways involved in HIV replication appear to be PKCtheta-, CARMA1-, and WASp-independent. Treatment with Cyclosporin A (CsA) further relieved the pre-integration block. However, transcription of HIV-1 RNA was still reduced in mouse CD4(+) T cells despite expression of the hCyclin T1 transgene. Additional post-transcriptional defects were observed at the levels of Gag expression, Gag processing, Gag release and virus infectivity. Together, these post-integration defects resulted in a dramatically reduced yield of infectious virus (300-500 fold) after a single cycle of HIV-1 replication. This study implies the existence of host factors, in addition to those already identified, that are critical for HIV-1 replication in mouse cells. This study also highlights the differences between primary T cells and cell lines regarding pre-integration steps in the HIV-1 replication cycle.

Genetic diversity and systematic evolution of Chinese domestic ducks along the Yangtze-Huai River.

To investigate the population structure and systematic evolution of the domestic duck in China, we sequenced the 667 bp mitochondrial DNA (mtDNA) D-loop control region of 106 ducks from nine breeds along the Yangtze-Huai River. Of the total analyzed sites, 34 (5.1%) were polymorphic due to transitions, transversions, insertions, and deletions. Nucleotide content was 25.6% A, 33.3% C, 15.2% G, and 25.9% T. In total, 31 haplotypes were identified in the target region; of these, the major haplotype was A7, and nine haplotypes were shared by the tested ducks. The haplotype diversity (Hd) and average nucleotide diversity (Pi) were 0.798% and 0.28%, respectively. Hd was highest in the Jingjiang shelduck, followed by the Youxian and Enshi shelducks, and it was lowest in the Wendeng black duck. Nucleotide diversity (Dxy) among the nine breeds ranged from 0.139 to 0.433%, and the Kimura 2-parameter distances were 0.0013-0.0044. Molecular variance indicated that a very high proportion of the insignificant genetic variance was attributable to variations within breeds. Phylogenetic analysis of 31 haplotypes revealed only one distinct maternal lineage in the tested ducks, and no evidence was found of a contribution of the Anas zonorhyncha group B haplotype to the maternal origin of Chinese domestic duck breeds along the Yangtze-Huai.

Level of proinsulin in association with cardiovascular risk factors and sleep snoring.

AIM: To explore the relationship between the level of proinsulin with cardiovascular risk factors and sleep snoring. METHODS: Based on the random stratified sampling principle, 1 193 Chinese residents in Pizhou City, Jiangsu Province (530 males and 663 females, aged 35-59 years with an average age of 46.69 years) were recruited. Their sleep snoring habits were investigated. Biotin-avidin based double mAbs ELISA was used to detect specific insulin and proinsulin, and a risk factor score was established to evaluate the individuals according to the number of their risk factors. RESULTS: The results of Spearman correlation analysis and covariate ANOVA analysis after age and sex were controlled, indicated that not only the level of proinsulin (r = 0.156, P = 0.000, F = 5.980 P = 0.000), but also cardiovascular risk factors score (r = 0.194, P = 0.000, F = 11.135, P = 0.000) significantly associated with the frequency of sleep snoring, and the significant relationship between true insulin and frequency of sleep snoring was only shown in the covariate ANOVA analysis (F = 2.868, P = 0.022). The result of multivariate stepwise logistic regression after age, sex, body mass index, waist circumference and true insulin were controlled showed that proinsulin (division by interval of quartile) was an independent risk factor for sleep snoring (OR = 1.220, 95%CI: 1.085-1.373, P = 0.001). CONCLUSION: The interaction of cardiovascular risk factors clustering, high proinsulin level and sleep breathing disorder may be a syndrome, which has not been recognized in human beings so far.

Nonpolar and short side chain groups at C-11beta of estradiol result in antiestrogens.

We have previously found that esters of 11beta-estradiol carboxylates are transformed from an estrogen into an antiestrogen when the 11beta-side chain is increased in length from four to five non-hydrogen atoms (n > or = 5). To understand the structural requirements for this transformation and obtain metabolically stable analogues that are not susceptible to esterase cleavage, we have synthesized other compounds having an 11beta-side chain composed of other functional groups: ketones, amides, ethers, and thiono esters. With the exception of amides, which bind poorly to the estrogen receptor (ER), all of these compounds exhibit antiestrogenic action when the side chain length is n > or = 5. Ethers (n > or = 5), studied in more detail, inhibit the action of estradiol with either ERalpha or ERbeta. In rat uteri they are estrogen antagonists/weak agonists and decrease the concentration of cholesterol in blood (an hepatic estrogenic action). Thus, these short chain and nonpolar 11beta-analogues of estradiol have tissue specific antiestrogenic/estrogenic actions, characteristics of selective estrogen receptor modulators.

Significant association of insulin and proinsulin with clustering of cardiovascular risk factors.

AIM: To investigate the association between true insulin and proinsulin and clustering of cardiovascular risk factors. METHODS: Based on the random stratified sampling principles, 1196 Chinese people (533 males and 663 females, aged 35-59 years with an average age of 46.69 years) were recruited. Biotin-avidin based double monoclonal antibody ELISA method was used to detect the true insulin and proinsulin, and a risk factor score was set to evaluate individuals according to the number of risk factors. RESULTS: The median (quartile range) of true insulin and proinsulin was 4.91 mIu/L (3.01-7.09 mIu/L) and 3.49 pmol/L (2.14-5.68 pmol/L) respectively, and the true insulin level of female subjects was significantly higher than that of male subjects (P = 0.000), but the level of proinsulin displayed no significant difference between males and females (P = 0.566). The results of covariate ANOVA after age and sex were controlled showed that subjects with any of the risk factors had a significantly higher true insulin level (P = 0.002 for hypercholesterolemia, P = 0.021 for high low-density lipoprotein cholesterol, P = 0.003 for low high-density lipoprotein cholesterol, and P = 0.000 for other risk factors) and proinsulin level (P = 0.001 for low high-density lipoprotein cholesterol, and P = 0.000 for other risk factors) than those with no risk factors. Furthermore, subjects with higher risk factor scores had a higher true insulin and proinsulin level than those with lower risk factor scores (P = 0.000). The multiple linear regression models showed that true insulin and proinsulin were significantly related to cardiovascular risk factor scores respectively (P = 0.000). CONCLUSION: True insulin and proinsulin are significantly associated with the clustering of cardiovascular risk factors.

Estrogen to antiestrogen with a single methylene group resulting in an unusual steroidal selective estrogen receptor modulator.

Selective estrogen receptor (ER) modulators (SERMs) are important therapeutic agents for breast cancer prevention and treatment. We have synthesized two analogs, E11-2,1 [methyl-(3,17beta-dihydroxyestra-1,3,5(10)-triene-11beta-yl)acetate] and E11-2,2 [ethyl-(3,17beta-dihydroxyestra-1,3,5(10)-triene-11beta-yl)acetate], the methyl and ethyl esters of an estradiol analog, substituted in the B ring at C-11beta with a carboxymethyl group. The shorter methyl ester, E11-2,1, has high ER affinity and high estrogenic potency in the Ishikawa estrogen cell bioassay, whereas the longer ethyl ester, E11-2,2, has even higher ER affinity, but little or no estrogenic activity. We found that this minor change of one methylene group transforms a potent estrogenic agonist into an antagonist in vitro with either ER alpha or beta. In the rat, E11-2,2 acts as a SERM in the uterus, where it inhibits estradiol-induced proliferation, and as an estrogen agonist in the liver and skeleton, where it decreases plasma cholesterol and increases bone growth. The characteristic feature of antiestrogens, including SERMs, is a long and polar side-chain that prevents agonist-induced conformation of helix 12 of ER. E11-2,2 with its short, nonpolar side-chain, lacks this critical structure, presenting the possibility that it might act through a unique mechanism.

[Synthesis and nNOS inhibitory activity of benzenealkyl isothiourea compounds].

AIM: To search for novel compounds with potent nNOS inhibitory activity for the treatment of Alzheimer's disease. METHODS: The target compounds were obtained by introducing benzenealkyl groups into the structure of isothioureas. nNOS inhibitory activity assays were conducted for the target compounds. RESULTS: Sixteen benzenealkyl isothiourea compounds (I1-16) were synthesized by three different synthetic methods from benzylamine (1) or (substituted) phenethylamine (2). Compounds I1-6 were synthesized from 1 or 2 by reaction with benzoyl isothiocyanate to form the corresponding benzoylthioureas 3 or 4, followed by hydrolysis with 10% sodium hydroxide solution, then S-alkylation with methyl iodide or ethyl iodide. I7-14 were synthesized from 1 or 2 by reaction with methyl isothiocyanate to form the corresponding 1, 3-disubstituted thioureas 7 or 8 which were S-alkylated with methyl iodide or ethyl iodide. I15 and I16 were synthesized from 2 by reaction with dimethyl cyanodithioimidocarbonate. The structures of compounds I1-16 were confirmed by MS, IR, 1HNMR and elementary analysis. The results of preliminary pharmacological test showed that all compounds possessed nNOS inhibitory activity, among which compounds I8, I12 and I14 had good activity. CONCLUSION: Compounds I8, I12 and I14 showed superior pharmacological profiles to the control compound S-methyl-N-(4-methoxyphenyl) isothiourea. The IC50 values of compounds I8, I12 and I14 inhibiting nNOS were 8.13 x 10(-7) mol.L-1, 1.74 x 10(-7) and 2.23 x 10(-7) mol.L-1 respectively, and it is worth further studying.

Synthesis and evaluation of B-, C-, and D-ring-substituted estradiol carboxylic acid esters as locally active estrogens.

We have synthesized derivatives of estradiol that are structurally modified to serve as "soft" estrogens and act within a geographically limited area of the body; estrogens without systemic action. We have previously shown with 16alpha-substituted analogues of estradiol that carboxylates proximal to the steroid ring neither bind to the estrogen receptor nor activate estrogen-responsive genes. However, when the carboxylic acid is masked as an ester, they bind to the receptor and stimulate estrogenic responses. Enzymatic hydrolysis through nonspecific esterases can inactivate these estrogens and thereby limit their area of action. Here, we describe our continued studies to design "soft" estrogens by synthesizing carboxylic acid esters of estradiol at the 7alpha-, 11beta-, and 15alpha-positions in the steroid nucleus at which bulky substituents are accommodated by the estrogen receptor. These compounds were tested for estrogen receptor binding (estrogen receptors alpha and beta), stimulation of an estrogen sensitive gene in Ishikawa cells in culture, and as substrates for enzymatic hydrolysis. Likely candidates were tested in in vivo assays for systemic and local estrogenic action. The biological studies showed that regardless of the point of attachment, all of the short-chain carboxylic acids, C-1 to C-3, were devoid of hormonal action, while many of the esters were estrogenic. The site on the steroid nucleus had great influence on hormonal activity and esterase hydrolysis. Formate esters at 7alpha and 15alpha were good estrogens, but lengthening the chain to acetate dramatically decreased hormonal activity. However, the 7alpha-formate esters were not enzymatically hydrolyzed. At 11beta, the acetate (methyl ester) was an effective estrogen, but increasing the chain length to propionate dramatically reduced hormonal activity. In general, the length of the alcohol from methyl to butyl had only a small effect on receptor binding, and as the size of the alcohol increased, so did esterase hydrolysis. One exception was the 11beta-acetate esters where increasing the alcohol moiety from methyl to ethyl eliminated estrogenic activity (Ishikawa cells) without affecting estrogen receptor binding. Several of the esters were tested in vivo, and two, the methyl and ethyl esters of estradiol-15alpha-formate, appeared to have the requisite properties (high local and low systemic activity) of superior "soft" estrogens.

Synthesis of halogen-substituted pyridyl and pyrimidyl derivatives of [3,2-c]pyrazolo corticosteroids: strategies for the development of glucocorticoid receptor mediated imaging agents.

Ligands for the glucocorticoid receptor labeled with high-energy isotopes are highly desired for their potential applications in nuclear medical studies of the brain where the dysregulation of this receptor system is thought to be involved in various neurodegenerative disorders. Analogues of the glucocorticoid cortivazol have previously been prepared as target compounds for labeling with high-energy isotopes. However, the phenyl rings of arylpyrazoles of this type are not sufficiently activated for nucleophilic substitution reactions that are generally required for the synthesis of radiohalogenated analogues. Since suitably substituted aromatic nitrogen heterocyclic groups are amenable to nucleophilic substitution, the goal of this study was the synthesis of pyridylpyrazolo and pyrimidylpyrazolo analogues similar to cortivazol that could be labeled with radiohalogens in the pyridine or pyrimidine rings. We describe the synthesis of several [3,2-c]pyrazolo steroids containing pyridyl, halopyridyl, and pyrimidyl substituents at the 2' position of the pyrazole ring. These compounds were tested for binding to the glucocorticoid receptor and for biological activity in glucocorticoid responsive HeLa cells grown in tissue culture. Of the pyridyl and pyrimidyl derivatives, 2'-(3-pyridyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxopregn-4-eno[3,2-c]pyrazole showed superior activity in both assays and it was used as the basis for the synthesis of several analogues that were halogenated in the pyridine ring. These halogenated compounds were all tested for their binding to the glucocorticoid receptor and for their biological activity. One, a fluorinated compound 2'-(2-fluoro-5-pyridyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxopregn-4-eno[3,2-c]pyrazole had excellent activity, considerably better than the potent glucocorticoid dexamethasone. Most importantly, fluorination was achieved using a nucleophilic exchange reaction, a method that is adaptable to radiolabeling with the positron-emitting isotope fluorine-18. Thus, considering its superior biological activity and adaptability for facile radiosynthesis, this target compound has the potential for imaging of glucocorticoid receptor containing tissues using positron emission tomography.