The LHRH antagonist cetrorelix: a review

In those clinical situations in which an immediate and profound suppression of gonadotrophins is desired, LHRH agonists have the disadvantage of producing an initial stimulatory effect on hormone secretion. Therefore, the use of GnRH antagonists which cause an immediate and dose-related inhibition of LH and FSH by competitive blockade of the receptors is much more advantageous. One of the most advanced antagonist produced to date is Cetrorelix, a decapeptide which has been shown to be safe and effective in inhibiting LH and sex-steroid secretion in a variety of animal species and in clinical studies as well. Clinical trials in patients suffering from advanced carcinoma of the prostate, benign prostate hyperplasia, and ovarian cancer are currently in progress and have already shown the usefulness of this new treatment modality. In particular, the concept that a complete suppression of sex-steroids may not be necessary in indications such as uterine fibroma, endometriosis and benign prostatic hyperplasia represents a promising novel perspective for treatment of these diseases. Following completion of phase III trials in controlled ovarian stimulation for IVF regimens, Cetrorelix was given marketing approval and, thus, became the first LHRH antagonist available clinically.     

Patterns of impaired oral health‐related quality of life dimensions

How dental patients are affected by oral conditions can be described with the concept of oral health‐related quality of life (OHRQoL). This concept intends to make the patient experience measurable. OHRQoL is multidimensional, and Oral Function, Oro‐facial Pain, Oro‐facial Appearance and Psychosocial Impact were suggested as its four dimensions and consequently four scores are needed for comprehensive OHRQoL assessment. When only the presence of dimensional impact is measured, a pattern of affected OHRQoL dimensions would describe in a simple way how oral conditions influence the individual. By determining which patterns of impact on OHRQoL dimensions exist in prosthodontic patients and general population subjects, we aimed to identify in which combinations oral conditions’ functional, painful, aesthetical and psychosocial impact occurs. Data came from the Dimensions of OHRQoL Project with Oral Health Impact Profile (OHIP)‐49 data from 6349 general population subjects and 2999 prosthodontic patients in the Learning Sample (N = 5173) and the Validation Sample (N = 5022). We hypothesised that all 16 patterns of OHRQoL dimensions should occur in these individuals who suffered mainly from tooth loss, its causes and consequences. A dimension was considered impaired when at least one item in the dimension was affected frequently. The 16 possible patterns of impaired OHRQoL dimensions were found in patients and general population subjects in both Learning and Validation Samples. In a four‐dimensional OHRQoL model consisting Oral Function, Oro‐facial Pain, Oro‐facial Appearance and Psychosocial Impact, oral conditions’ impact can occur in any combination of the OHRQoL dimensions.     

Association between perceived oral and general health

Objectives

The aim of this study was to determine the magnitude of the association between perceived oral and general health-related quality of life (O/HRQoL) in the German general population and to compare it with the correlation of both constructs in dental patients.

Methods

OHRQoL was assessed using the OHIP-49 and HRQoL using the SF-36 in a sample (N = 811) representative of the adult general population of Germany (age: 18–99 years), and in a sample (N = 313) of consecutive adult dental patients at least 18 years of age seeking prosthodontic care or attending their annual checkup. Correlation between OHRQoL and HRQoL was computed using structural equation modelling-based confirmatory factor analysis and path analysis. Based on the correlation coefficients, the coefficients of determination (r²) were calculated.

Results

Correlation between OHRQoL and HRQoL after partialling out effects of age, gender and level of depression in general population subjects was rho = 0.28 resulting in an explanation of the variance of HRQoL by OHRQoL of 7.8%. In dental patients the correlation coefficient was somewhat lower (rho = 0.24) corresponding to an explanation of the variance of HRQoL by OHRQoL of 5.6%. Difference between correlation coefficients was not significant (p = 0.514).

Conclusion

Our findings provide evidence for the inseparable, intertwined relationship between perceived oral and general health.     

Oral health and access to dental care – a comparison of elderly migrants and non-migrants in Germany

Objectives: To compare oral health, access barriers to dental care, oral health behavior and oral hygiene behavior of elderly German residents with and without immigration background.

Design: In this cross-sectional explorative study, a convenience sample (N?=?112, age?≥?60 years, 54% immigrants) was recruited in four dental practices in Hamburg, Germany. Oral health was assessed with Decayed/Missing/Filled Teeth (DMFT), Papillary Bleeding Index (PBI), and Approximal Plaque Index (API). Dental health was operationalized as number of decayed teeth, and poor oral hygiene based on a PBI?≥?40%. Access barriers and oral health behavior were assessed with a standardized questionnaire.

Results: While caries experience was similar in migrants and non-migrants (DMFT mean: 24.8 vs. 23.4, n.s.), significantly more teeth were decayed (5.3 vs. 2.1, p?p?=?0.002) and PBI (46.3% vs. 30.5%, p?=?0.016) were significantly higher in migrants. After adjusting for age, sex, income, education, and number of teeth, migrants still had on average 3 decayed teeth more than non-migrants. However, impact of migration background on poor oral health changed from OR?=?3.61 (p?=?0.007) to OR?=?1.05 (n.s.) after adjusting for confounders, mainly due to lower income in migrants. Fewer migrants had visited a dentist within the past 12 months, and migrants were less likely to have a regular dentist that they visit and more often indicated language or cost barriers than non-migrants.

Conclusion: Elderly German migrants have higher treatment needs than non-migrants. Likely causes are poorer oral hygiene and lower utilization of dental care services. Specific prevention programs targeting migrants are warranted to improve oral health in this disadvantaged group.     

Synthesis and biological evaluation of analogues of the peptaibol ampullosporin A

A series of analogues of the fungal peptaibol type metabolite ampullosporin A containing modifications in the C and N terminus as well as alpha-aminoisobutyric acid (Aib) substitutions in different positions of the peptide were synthesized by solid phase synthesis using the 9-fluorenylmethyloxycarbonyl strategy. Depending on the sequence position, couplings were performed with 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate/1-hydroxybenzotriazole and tetramethylfluoroformamidinium hexafluorophosphate, respectively. The structures of the target peptides were analyzed by electrospray ionization mass spectrometry and chromatographic methods (high-performance liquid chromatography, thin-layer chromatography). The biological activities of these compounds have been evaluated by assaying their potencies for the induction of pigment formation on the fungus Phoma destructiva as well as for the induction of hypothermia and inhibition of locomotoric activity in mice and were compared to the naturally occurring ampullosporins. Native ampullosporin A and analogues with C-terminal Leu or Leu-NH(2) showed comparable activity in the pigmentation assay. Similarly, the ampullosporin A analogues with N-terminal aromatic amino acid residues, such as D-Trp and Tic, also have high potency for pigment formation. The peptides containing structural modifications of ampullosporin A by systematic replacement of Aib by Ala (Ala scan) displayed moderate or high activity in the pigmentation assay, whereas simultaneous substitution of all Aib residues by Ala and Ile, respectively, or by insertion of nonaromatic residues into position 1 resulted in a loss of the effect on P. destructiva. Most of the compounds with no or weak activity in the microbial assay were not active in the hypothermic test, too, except the compound with 1-amino-1-cyclohexane carboxylic acid in position 4 instead of Aib. However, only a few compounds with high potency for pigmentation induction were found to produce strong hypothermia in mice. Thus, in contrast to the native ampullosporins, we succeeded to a certain degree in differentiation of the bioactivities with our synthetic analogues.