Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.

The first asymmetric synthesis of (S)- and (R)-5-hydroxythalidomides, one of thalidomide's major metabolites, was achieved using HMDS/ZnBr(2)-induced imidation as a key reaction. 5-Hydroxythalidomide was found to be configurationally more stable than thalidomide at physiological pH. Stereochemical biological effects of thalidomide and 5-hydroxythalidomide on anti-angiogenesis and antitumor activities were also investigated using racemic and pure enantiomers.

Enzymatic resolution and evaluation of enantiomers of cis-5'-hydroxythalidomide.

The straightforward synthesis of both enantiomers of cis-5'-hydroxythalidomide, a major metabolite of thalidomide, has been accomplished by enzymatic kinetic resolution of a racemic substrate catalyzed by Pseudomonas stutzeri lipase TL. cis-5'-Hydroxythalidomide shows resistance to racemization (and epimerization) at physiological pH. A tube formation assay to assess the ability to inhibit angiogenesis revealed that cis-5'-hydroxythalidomides are inactive.

Difference of pharyngeal morphology and mechanical property between OSAHS patients and normal subjects.

OBJECTIVE: The intrinsic properties such as baseline caliber and compliance of upper airway are thought to be important in the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS). Our study was designed to detect the difference of baseline caliber (morphological property) of pharynx during both wakefulness and sleep, and difference of pharyngeal compliance (mechanical property) between OSAHS patients and normal subjects. METHODS: CT scan was performed on 7 normal subjects and 13 OSAHS patients when they are awake, during drug-induced sleep with minimally effective therapeutic pressure (P(eff)), 0 cmH2O, and critical pressure (P(crit)) being given via a nose mask system, respectively. 3D images of pharyngeal airway were reconstructed, and volume of each subdivision of pharynx was measured. Volume, average area and compliance of each subdivision and in total were compared between the two groups. RESULTS: The OSAHS group was shown to have a smaller average area at upper (1.20+/-0.26 cm2 versus 1.57+/-0.17 cm2, p<0.05) and middle part of pharynx (1.89+/-0.52 cm2 versus 2.58+/-0.27 cm2, p<0.05) during wakefulness. During sleep, this difference was shown to be even more obvious at upper part (0.77+/-0.30 cm2 versus 1.45+/-0.18 cm2, p<0.01); and middle part, (1.15+/-0.47 cm2 versus 2.44+/-0.26 cm2, p<0.01). The average area during wakefulness and sleep was also shown to be highly correlated. OSAHS group had a higher compliance at middle part (0.28+/-0.15 cmH2O(-1) versus 0.13+/-0.07 cmH2O(-1), p<0.05) of pharynx. CONCLUSION: We conclude that OSAHS patients have a narrower and more collapsible upper airway than normal subjects do, the caliber data obtained during wakefulness could reflect the baseline caliber during sleep, and our method is valid to evaluate both morphology and function of upper airway.

[Adjuvant chemotherapy with TS-1 for head and neck cancer--side effect of two-week application followed by one-week rest regimen].

Multimodality therapy incorporated with radiotherapy, surgery and chemotherapy are used in the treatment of head and neck cancer in order to improve the local control and survival rate. TS-1, a newly developed oral antitumor agent which could achieve the same therapeutic concentration as that of 5-FU under continuous and intravenous treatment, has been used as adjuvant therapy for carcinomas in recent years. We presented our experience applying a new regimen of TS-1 and its side effects. TS-1 has been applied for head and neck carcinomas since 2001. The oral application of TS-1 has been used in 32 cases of head and neck cancer in our department since 2003, and the agent has been applied in 22 of 32 cases as adjuvant therapy. The primary sites of malignancy included hypopharyngx (7 cases), larynx (6 cases), maxillary sinus (2 cases), oropharynx (2 cases), oral cavity (4 cases), submandibular gland (1 case) and one case in which the primary site was unknown. A regimen of four-week application followed by two-week rest had been used in 6 cases in the first part of this trial. However, a high frequency of blood toxicity was found from the third week, requiring alteration of the protocol. Thus, a new regimen of two-week application followed by one week rest was thereafter used in the other 16 cases. Blood toxicity was found in 66.7% of those cases receiving a four-week application followed by two-week rest regimen. In the 16 cases receiving the two-week application followed by one-week rest regimen, only one case showed grade 2 leucopenia while continuous application for more than eight weeks was possible in 9 cases. Mild macrocytic anemia was found in some of these cases, however none of which required any necessary interruption of the treatment. Side effects other than blood toxicity, such as edema or pigmentation of lower limbs, erythema of skin and diarrhea, were found in the other cases, requiring suspension of the treatment. But the subsequent application was possible after a break or decreasing the dosage. We concluded that the new regimen of two-week application followed by one-week rest is less likely to be interrupted by the side effects and is safer to be used outpatiently, compared with the four-week application followed by two-week rest.