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Premature luteinization of one or more developing follicles complicates 1–2 % of controlled ovarian stimulation cycles for assisted reproduction. The management of this complication is controversial, with cycle cancellation likely representing the most commonly used strategy. The aim of this study was to evaluate the efficacy of the “freeze-all” policy—where the entire cohort of blastocysts is cryopreserved for subsequent frozen-thawed embryo transfer—in treating cases of premature luteinization. Patients experiencing premature luteinization during controlled ovarian stimulation—identified by extremely high progesterone levels at induction (P levels ≥3.0 ng/ml and/or P/estradiol ratio ≥1, n= 42)—were included in a “freeze-all” program and compared to controls undergoing a “freeze-all” program with normal progesterone levels at induction (P < 1.5 ng/ml, n= 67). Blastulation rate was comparable between patients with premature luteinization and controls (48.1 ± 20.5 % in Cases vs. 52.3 ± 24.9 % in Controls, p= 0.36). Ongoing pregnancy rates after the first frozen-thawed embryo transfer (38.1 % in Cases and 41.0 % in Controls, p= 0.83) and cumulative ongoing pregnancy rates after three frozen-thawed embryo transfer cycles (40.5 % in Cases vs. 47.8 % in Controls, p= 0.55) were also similar. These results show that extremely marked progesterone elevation throughout controlled ovarian stimulation does not impair blastocyst development and implantation potential in the context of a “freeze-all” strategy. Based on this, adoption of the “freeze-all” strategy represents a valuable tool in treating premature luteinization. In contrast, cycle cancellation—likely the most frequently used method for management of this complication—currently represents a misconduct.

PurposeTo determine the mean 24-h intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) characteristics of newly diagnosed, previously untreated, Caucasian, normal tension glaucoma (NTG) patients and to identify relationships between these features and visual field (VF) loss at diagnosis.MethodsConsecutive newly diagnosed NTG patients underwent 24-h habitual IOP and blood pressure (BP) monitoring. Parameters from pooled measurements obtained in the sitting (0800–2200 hours) and supine (1200–0600 hours) positions were compared and associations were sought with VF mean deviation (MD) and pattern standard deviation (PSD).ResultsSixty-two Caucasian NTG patients (24 men and 38 women) successfully completed circadian IOP and BP monitoring. In habitual position, 8 subjects (12.9%) exhibited a diurnal acrophase, 42 subjects (67.7%) demonstrated a nocturnal acrophase, one subject (1.6%) showed a flat rhythm and 11 patients (17.7%) revealed a biphasic/polyphasic rhythm. Nighttime MOPP values (supine position) were significantly greater than diurnal values (sitting position); (P<0.001). No association could be demonstrated between glaucomatous damage, as indicated by VF parameters, and either mean habitual 24-h IOP (P=0.20 and P=0.12 for MD and PSD, respectively), or habitual 24-h MOPP (P=0.96 and 0.29, for MD and PSD, respectively).ConclusionsIn this cohort of Caucasian NTG patients, most patients exhibited a nocturnal IOP acrophase when evaluated in a habitual position. No association was found between 24-h IOP or MOPP and VF damage.

An azaspiro[5.5]undecadiene corresponding to a subunit of the shellfish toxin gymnodimine was synthesized by Diels−Alder cycloaddition. One member of the pair of stereoisomeric adducts was transformed to a spiroimine, which will serve as the core around which the macrocyclic portion of the toxin will be assembled.

A bis-(2,6-dichlorobenzyl) ether is shown to undergo efficient and highly stereoselective intramolecular iodoetherification to yield a cis-2,5-disubstituted tetrahydrofuran, thus providing a powerful illustration of a stereodirecting effect first noted by Rychnovsky and Bartlett. The tetrahydrofuran was transformed into a subunit suitable for incorporation into the shellfish toxin gymnodimine.

A new strategy to control the enantioselectivity of Lewis acid catalyzed reactions has been investigated. The use of N-acryloyl-1,3-benzoxazol-2-(3H)-ones substituted at position 4 leads to the formation of diastereomeric complexes as a result of the presence of a chiral axis. The stereochemical outcome of the reaction is controlled by the chiral catalyst and by the chiral axis, leading to high enantioselectivity improvements and, in one case, to an inversion of enantioselectivity.

Several studies suggest that nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to cardiovascular mortality. Furthermore, NO synthesis is impaired in glutathione (GSH)-depleted human umbilical vein endothelial cells and GSH is reduced in patients with type 2 diabetes mellitus (T2DM). We tested the hypothesis that treatment with GSH may improve platelet constitutive NO sinthase (cNOS) activity in patients with T2DM. Fifteen patients with T2DM underwent a treatment with GSH 600 mg/day im for 10 days. With respect to the basal values on the 10thday of treatment, the red blood cell GSH concentration and platelets cNOS increased (1.4±0.1 vs1.9±0.1 μmol/1010RBC, p<0.001 and 0.7±0.1 vs2.9±0.2 fmol·min−1·10−9PLTs, p<0.001, respectively) and the plasma PAI-1 levels diminished (81.4±3.7 vs68.7±4.0 ng/ml, p<0.002). A negative correlation between the cNOS and the PAI-1 was found on the basal values. After a wash-out of 30 days the values of red blood cell GSH concentration, platelet cNOS activity and PAI-1 Ag returned to the basal levels. These data suggest that the administration of GSH, in patients with T2DM, is able to improve platelet cNOS activity together with a reduction of PAI-1.

Purpose: A randomized clinical trial to assess ocular hypotensive effect of sublingual administration of timolol was performed. Patients and methods: Seventeen (9 male, 8 female; age range 45 to 68 years) with bilateral ocular hypertension were selected for the study. Each patient was evaluated with regard to IOP, arterial blood pressure and heart rate before and after each of the following experimental treatment: unilateral ocular administration of 20 μl of 0.5% timolol solution; sublingual administration of 20 μl of 0.5% timolol solution; unilateral ocular administration of 20 μl of saline solution (placebo); sublingual administration of 20 μl of saline solution (placebo). The sequence of the treatments and the eye topically treated were randomly chosen. At least four weeks wash-out elapsed between each experimental treatment. Results: Our results showed that sublingual administration of timolol was able to induce a bilateral significant reduction of the IOP. This reduction was not statistically different from that obtained in the eye treated with timolol. A significantly greater reduction of the IOP was obtained by sublingual timolol than in the contralateral eye after unilateral topical administration of timolol solution. No significant modification of arterial blood pressure and heart rate were evidenced after the treatment. Conclusions: Sublingual administration seems to be a new interesting way for reducing the IOP. Long term studies are required in order to test efficacy and safety of this new treatment.

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