Nuclear estrogen receptor beta in lung cancer: expression and survival differences by sex.

PURPOSE: A role for estrogens in determining lung cancer risk and prognosis is suggested by reported sex differences in susceptibility and survival. Archival lung tissue was evaluated for the presence of nuclear estrogen receptor (ER)-alpha and ER-beta and the relationship between ER status, subject characteristics, and survival. EXPERIMENTAL DESIGN: Paraffin-embedded lung tumor samples were obtained from 214 women and 64 men from two population-based, case-control studies as were 10 normal lung autopsy samples from patients without cancer. Nuclear ER-alpha and ER-beta expression was determined by immunohistochemistry. Logistic regression was used to identify factors associated with ER positivity and Cox proportional hazards models were used to measure survival differences by ER status. RESULTS: Neither tumor (0 of 94) nor normal (0 of 10) lung tissue stained positive for ER-alpha. Nuclear ER-beta positivity was present in 61% of tumor tissue samples (170 of 278; 70.3% in men and 58.3% in women) and 20% of normal tissue samples (2 of 10; P = 0.01). In multivariate analyses, females were 46% less likely to have ER-beta-positive tumors than males (odds ratio, 0.54; 95% confidence interval, 0.27-1.08). This relationship was stronger and statistically significant in adenocarcinomas (odds ratio, 0.40; 95% confidence interval, 0.18-0.89). Women with ER-beta-positive tumors had a nonsignificant 73% (P = 0.1) increase in mortality, whereas men with ER-beta-positive tumors had a significant 55% (P = 0.04) reduction in mortality compared with those with ER-beta-negative tumors. CONCLUSIONS: This study suggests differential expression by sex and influence on survival in men of nuclear ER-beta in lung cancer, particularly in adenocarcinomas.     

Allosteric Modulators of Class B G-Protein-Coupled Receptors

Class B GPCR’s are activated by peptide ligands, typically 30-40 amino acid residues, that are involved in major physiological functions such as glucose homeostasis (glucagon and glucagon-like peptide 1), calcium homeostasis and bone turnover (parathyroid hormone and calcitonin), and control of the stress axis (corticotropin-releasing factor). Peptide therapeutics have been developed targeting these receptors but development of nonpeptide ligands, enabling oral administration, has proved challenging. Allosteric modulation of these receptors provides a potential route to developing nonpeptide ligands that inhibit, activate, or potentiate activation of these receptors. Here the known mechanisms of allosteric modulators targeting Class B GPCR’s are reviewed, particularly nonpeptide antagonists of the corticotropin-releasing factor 1 receptor and allosteric enhancers of the glucagon-like peptide-1 receptor. Also discussed is the potential for antagonist ligands to operate by competitive inhibition of one of the peptide binding sites, analogous to the Charniere mechanism. These mechanisms are then used to discuss potential strategies and management of pharmacological complexity in the future development of allosteric modulators for Class B GPCR’s.     

The utilisation of superficial venous surgery for chronic venous insufficiency by the U.K. Asian population.

BACKGROUND: The epidemiology of superficial venous disease is relatively well defined in the U.K. Caucasian population. By contrast, there are currently no data available for Asians, who comprise 3.6% of the U.K., and 14.1% of this institution's catchment population. The aim of this study was to compare surgery for superficial venous disease in Caucasians and Asians in this institution, in the context of our local population. METHODS: A prospectively gathered database of all 2011 superficial venous operations performed between January 1997 and April 2002 was retrospectively analysed with regard to ethnicity. The ethnic, gender and age composition of our catchment area was determined from U.K. census data. The full institutional records of 100 Asian and 100 randomly selected age and sex-matched Caucasian patients were compared in a case control study. RESULTS: After adjusting for age and gender according to census data, Asians were 40% less likely to undergo superficial venous surgery (SVS). Considering the 2011 operated patients as a whole, Asians were significantly younger and more likely to be male. In the case control study, Asians were significantly less likely to be operated for recurrent disease and significantly more likely to be operated for advanced disease. CONCLUSIONS: Although Asians are significantly less likely to undergo SVS; those that do are more likely to be young, male and operated for skin changes and ulcers. This strongly suggests that the under-representation of Asians is due to cultural, genetic or environmental factors and unmet health care need, rather than a lower prevalence of clinically significant venous disease in the Asian population.     

Benign osteoblastoma of the occipital bone: Case report and literature review

We present a case of benign osteoblastoma of the occipital bone. Benign osteoblastoma is an uncommon primary bone tumor, which usually involves the vertebrae and the long bones. This tumor rarely develops in the calvaria, showing a preference for the temporal and frontal bones when it does. To the best of our knowledge, this case is only the eighth reported case of benign osteoblastoma confined to the occipital bone. A 20‐year‐old male presented with a mild tender mass lesion of the occipital area, just below the lambda. Plain X‐ray films and CT scans demonstrated an osteolytic mass surrounded by the sclerotic rim within the diploic space. MRI proved to be effective for the evaluation of the intracranial and intraosseous extensions of the tumor. However, it was very difficult to formulate a differential diagnosis against other osteoblastic tumors, or osteoid osteoma, in view of its radiological appearance. The final diagnosis was obtained by careful consideration of the histopathological characteristics of the tumor combined with its clinical and radiological features. Although generally regarded as benign, a complete resection is preferred over conventional curettage as this can guard against possible recurrence and malignant transformation.     

Physico-chemical properties and stability of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate

The physico-chemical properties of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate (Org 5222), a new potential antipsychotic compound, were studied by interpretation of its spectra (UV,IR,NMR,mass), X-ray analysis, thermal properties, solubilities and partition coefficient. Analytical methods such as GLC and TLC were developed for use in stability tests. Crystalline Org 5222 was shown to be stable with respect to heat. Only excessive exposure to light was shown to induce degradation of crystalline Org 5222. In solutions of pH 1, 4 and 7 only slight degradation was observed at high temperature or after exposure to light.     

Saponins from the roots ofPulsatilla koreana

From the roots ofPulsatilla koreana, three monodesmosides(pulsatilla saponins A, B and D) and two bisdesmosides(pulsatilla saponins F and H) were isolated. The structure of these saponins have been determined as hederagenin 3-O-α-L-rhamnopyranosyl(1→2)-α-L-arabinopyranoside(A), hederagenin 3-O-β-D-glucopyranosyl(1→4)-α-L-arabinopyranoside(B), hederagenin 3-O-α-L-rhamnopyranosyl (1→2)-[β-D-glucopyranosyl(1→4)]-α-L-arabinopyranoside(D), 3-O-α-L-rhamnopyranosyl(1→2)-α-L-arabinopyranosyl hederagenin 28-O-α-L-rhamnopyranosyl(1→4)-β-D-glucopyranosyl(1→6)-β-D-glucopyranosyl ester (F) and 3-O-α-L-rhamnopyranosyl(1→2)-[β-D-glucopyranosyl(1→4)]-α-L-arabinopyranosyl hederagenin 28-O-α-L-rhamnopyranosyl(1→4)-β-D-glucopyranosyl(1→6)-β-D-glucopyranosyl ester(H) on the basis of chemical and spectral studies. Pulsatilla saponin B is the first report of its presence in plants but saponins A, D, F, and H have recently been isolated from the same genusP. cernua.