Effect of oral administration of dydrogestrone versus vaginal administration of natural micronized progesterone on the secretory transformation of endometrium and luteal endocrine profile in patients with premature ovarian failure: a proof of concept

BACKGROUND: We aimed to explore the endometrial histology and endocrine profiles on day 21 of an artificial cycle in patients with premature ovarian failure (POF) treated with oral dydrogesterone (DG) or vaginal micronized progesterone. METHODS: The study was designed as a prospective pilot study at an academic reproductive medicine unit. Six POF patients were included in the study. After estrogen endometrial priming, patients were randomized to receive DG or progesterone in two subsequent cycles. The main outcome measure was the endometrial histology and the endocrine profiles on day 21 of the cycle. RESULTS: Development of endometrial glands corresponded to an early secretory phase in five out of six cases supplemented with DG (out-phase). In contrast, five out of six cases treated with micronized progesterone showed an endometrium corresponding to a mid-luteal phase (in-phase) (P = 0.021 versus DG). There was a significant difference in the mean progesterone value [8.6 versus 0.3 microg l(-1) (P = 0.013)], the mean LH value [12.9 versus 22.5 IU l(-1) (P = 0.049)] and the mean FSH value [13.0 versus 23.9 IU l(-1) (P = 0.047)] between the progesterone and DG group, respectively, on day 21 of the cycle. CONCLUSIONS: After estrogen endometrial priming in POF patients, exogenous vaginal micronized progesterone is more effective than oral DG in creating an 'in-phase' secretory endometrium and induces significantly higher progesterone and lower LH and FSH serum concentrations on day 21 of the cycle.     

Focus on HPV Infection and the Molecular Mechanisms of Oral Carcinogenesis

This study is focused on the epidemiological characteristics and biomolecular mechanisms that lead to the development of precancerous and cancerous conditions of oral lesions related to Human Papilloma Virus (HPV) infections. Current evidence from the literature demonstrates the role of HPV in potentially malignant oral disorders. Therefore, the underlying biomolecular processes can give arise, or contribute to, benign lesions as well as to oral carcinogenesis.     

Influence of apneic oxygenation on cardiorespiratory system homeostasis

Purpose

The aim of this study was to elucidate the magnitude of variations in oxygenation indices and the pattern of hemodynamic changes in response to the net effect of tracheal apneic oxygenation (AO) with a view to define the safe time limit of its application.

Methods

After obtaining Animal Research Ethics Committee approval, AO was applied in 12 piglets for 40 min. Arterial (a) and mixed venous (v) blood samples for oxygen (O₂) and carbon dioxide (CO₂) tension (PaO₂/PvO₂, PaCO₂/PvCO₂), O₂ saturation (SaO₂/SvO₂), pHa, base excess (BEa), and bicarbonate (HCO₃a) determination and for alveolar O₂ tension (PAO₂), PaO₂/FiO₂ and PaO₂/PAO₂ ratio, arterial–mixed venous O₂ content (AVDO₂), and O₂ extraction ratio (O₂ER) estimation were collected on anesthesia induction, 10, 20, 30, and 40 min during AO and 10 and 20 min after reconnection to the ventilator. Concomitant hemodynamic data were obtained.

Results

Besides PvO₂ and PAO₂, AO adversely influenced PaO₂ (248–113 mmHg), PaCO₂ (35–145 mmHg), PvCO₂, PaO₂/FiO₂, and PaO₂/PAO₂ in a time-depended fashion, whereas SvO₂, AVDO₂, and O₂ER were minimally affected. P(a ? v)CO₂ was reversed throughout AO. Acid–base status derangement, consisting of HCO₃a elevation, BEa widening, and acidemia (pH 6.9) maximized 40 min after AO. During AO, heart rate, systemic and pulmonary circulation pressures, and cardiac output were progressively elevated, whereas systemic vascular resistance was reduced. All the studied parameters reverted almost to baseline within the 20-min period of ventilator reconnection.

Conclusion

Tracheal AO for 40 min ensures acceptable blood oxygenation, promotes notable hypercapnic acidosis, and consequent transient hemodynamic alterations, which are almost completely reversible after reconnection to the ventilator.     

Are the measurements of water-filled and air-charged catheters the same in urodynamics?

Introduction and hypothesis

The aim of our study was to compare air-charged and water-filled catheters simultaneously in the measurement of the intravesical, abdominal and detrusor pressure during urodynamic investigations.

Methods

Consecutive women with lower urinary tract symptoms, referred for urodynamics were prospectively studied. Readings of intravesical pressure (p_ves), abdominal pressure (p_abd) and detrusor pressure (p_det), recorded by both the air-charged and water-filled catheters, were displayed simultaneously and compared at the end of filling, on standing, on sitting prior to voiding and at the maximum involuntary detrusor contraction. The signals (pressures) recorded by both types of catheter were compared using the Bland–Altman plot and paired samples t test.

Results

Twenty women with a mean age of 49 (range 36–72) were recruited. One patient with normal urodynamics was excluded in view of the poor quality trace. At each of the four comparison points, the air-charged catheters consistently produced higher mean pressures than the water-filled catheters. There were wide variations in the difference between the readings produced by the two types of catheter.

Conclusions

Pressures measured using air-charged catheters are not comparable with water-filled catheters and are therefore not interchangeable. Caution must be used when comparing urodynamic parameters using air-charged and water-filled catheters.     

Remineralization potential of fully demineralized dentin infiltrated with silica and hydroxyapatite nanoparticles

Objective

This study investigates the potential of a novel guided tissue regeneration strategy, using fully demineralized dentin infiltrated with silica and hydroxyapatite (HA) nanoparticles (NPs), to remineralize dentin collagen that is completely devoid of native hydroxyapatite.

Methods

Dentin blocks were fully demineralized with 4 N formic acid and subsequently infiltrated with silica and HA NPs. The remineralizing potential of infiltrated dentin was assessed following a twelve week exposure to an artificial saliva solution by means of TEM, EDS and micro-CT. Measurements were taken at baseline and repeated at regular intervals for the duration of the study to quantify the P and Ca levels, the mineral volume percentage and mineral separation of the infiltrated dentin specimens compared to sound dentin and non-infiltrated controls.

Results

Infiltration of demineralized dentin with nano-HA restored up to 55% of the P and Ca levels at baseline. A local increase in the concentration of calcium phosphate compounds over a period of twelve weeks resulted in a higher concentration in P and Ca levels within the infiltrated specimens when compared to the non-infiltrated controls. Remineralization of demineralized dentin with silica NPs by immersion in artificial saliva was the most effective strategy, restoring 20% of the P levels of sound dentin. Micro-CT data showed a 16% recovery of the mineral volume in dentin infiltrated with silica NPs and a significant decrease in the mineral separation to levels comparable to sound dentin.

Significance

Demineralized dentin infiltrated with silica NPs appears to encourage heterogeneous mineralization of the dentin collagen matrix following exposure to an artificial saliva solution.     

Simple and Robust Intravital Microscopy Procedures in Hybrid TIE2GFP-BALB/c Transgenic Mice

Purpose

The endeavor of deciphering intricate phenomena within the field of molecular medicine dictates the necessity to investigate tumor/disease microenvironment real-time on cellular level. We, hereby, design simple and robust intravital microscopy strategies, which can be used to elucidate cellular or molecular interactions in a fluorescent mouse model.

Procedures

We crossbred transgenic TIE2GFP mice with nude BALB/c mice, allowing the breeding of immunocompetent and immunodeficient mouse models expressing green fluorescent protein (GFP) in vascular endothelium. Then, we surgically exposed various tissues of interest to perform intravital microscopy.

Results

By utilizing simple tissue preparation procedures and confocal or two-photon microscopy, we produced high-resolution static snapshots, dynamic sequences, and 3D reconstructions of orthotopically grown mammary tumor, skin inflammation, brain, and muscle. The homogenous detection of GFP expressed by endothelial cells and a combination of fluorescence agents enabled landmarking of tumor microenvironment and precise molecular tagging.

Conclusion

Simple intravital microscopy procedures on TIE2GFP mice allowed a real-time multi-color visualization of tissue microenvironment, underlining that robust microscopy strategies are relatively simple and can be readily available for many tissues of interest.