[Clinical effects of free peroneal artery perforator flaps in repairing forefoot skin and soft tissue defect wounds assisted with three-dimensional computed tomography angiography].

Objective: To investigate the clinical effects of free peroneal artery perforator flaps in repairing forefoot skin and soft tissue defect wounds assisted with three-dimensional computed tomography angiography (3D-CTA). Methods: A retrospective observational study was conducted. From March 2017 to September 2019, 15 patients with skin and soft tissue defect wounds in the forefoot were treated in the Department of Burn and Plastic Surgery of Yidu Central Hospital of Weifang, including 12 males and 3 females, with age of 18-60 years. The wound area on admission was 3.0 cm×3.0 cm-9.0 cm×8.0 cm. The 3D-CTA examination before operation was performed to select the peroneal artery perforating vessels with appropriate length of vascular pedicle and good blood perfusion. According to the wound area and the perforating vessels of the peroneal artery located by 3D-CTA, the peroneal artery perforator flaps of 3.5 cm×3.5 cm-9.5 cm×8.5 cm carried with lateral sural cutaneous nerve was designed and cut, and the nerve was anastomosed with the nerve of the wound. The wound in the donor site of the flap was directly sutured or covered with medium-thickness skin graft from the thigh. The consistencies of type, diameter, and perforating position of perforating vessel of the peroneal artery detected by 3D-CTA before the operation with those of the actual measurement during operation were observed. The length of time for flap cutting and the survival of the flap after operation were recorded. During follow-up of 12 months after the operation, the patients were instructed to evaluate the foot function according to the Maryland foot function score standard, and the wound healing in the donor area and the occurrence of complications affecting the motor function of limb were observed. Data were statistically analyzed with paired sample t test. Results: The types of peroneal artery perforating vessels in patients measured during the operation were septocutaneous perforator of 12 cases, musculocutaneous perforator of 2 cases, and musculomuscular septal perforator of 1 case, which were consistent with those measured by preoperative 3D-CTA. The diameter of the peroneal artery perforating vessel measured by preoperative 3D-CTA was (1.38±0.17) mm, which was close to (1.40±0.19) mm measured during the operation (t=0.30, P>0.05). The horizontal distance from the starting point of the perforating vessel to the outer edge of the shank was (42±6) mm, and the vertical distance from the starting point of the perforating vessel to the level of the lateral ankle tip was (219±14) mm measured by preoperative 3D-CTA, which were respectively close to (43±6) and (221±15) mm of intraoperative measurement (with t values of 0.46 and 0.38, respectively, P>0.05). The length of time for cutting flap was (31±6) min. All flaps survived post operation without vascular crisis. During follow-up of 12 months after the operation, the foot function was evaluated as excellent in 11 cases, good in 3 cases, and fair in 1 case, the donor site wound healed well, the scar was not noticeable with no contracture, and the motor function of joints was not affected. Conclusions: Free peroneal artery perforator flap is one of the effective methods to reconstruct skin and soft tissue defect wounds in the forefoot, and the risk of surgery can be reduced when the anatomical location of the perforating vessels is confirmed by 3D-CTA.

[Clinical effects of autologous platelet rich plasma gel combined with vacuum sealing drainage techno-logy in repairing refractory wounds].

Objective: To investigate the clinical effects of autologous platelet rich plasma (PRP) gel in combination with vacuum sealing drainage (VSD) technology in repairing refractory wounds. Methods: From March 2011 to January 2015, 44 patients with refractory wounds meeting the inclusion criteria were recruited into VSD alone group, who were admitted to the Department of Burns and Plastic Surgery of the Yidu Central Hospital of Weifang and received intermittent VSD treatment. From February 2015 to September 2019, 43 patients with refractory wounds meeting the inclusion criteria were recruited into PRP+ VSD group, who were admitted to the same unit as above-mentioned and received PRP combined with intermittent VSD treatment. The retrospective cohort study was conducted. There were 24 males and 20 females with age of (37.5±2.2) years in VSD alone group, and there were 25 males and 18 females with age of (37.0±2.5) years in PRP+ VSD group. The wound exudate of patients in the two groups before and 7 and 14 d after the first treatment were collected for bacterial culture, and the positive rate of bacterial culture was calculated. The wound healing of patients in the two groups was observed on 7, 14, and 21 d after the first treatment, and the wound healing rate was calculated. The complete wound healing time of patients in the two groups was recorded. The degree of wound pain of patients in the two groups was evaluated by the Visual Analog Scale (VAS) before and 14 d after the first treatment. The scar hyperplasia of patients in the two groups was evaluated by the Vancouver Scar Scale (VSS) in 1 and 2 months after the wound healed completely. The occurrence of adverse reactions of patients in the two groups during the whole period of treatment was observed and the incidence of adverse reactions was calculated. Data were statistically analyzed with analysis of variance for repeated measurement, chi-square test, paired t test, and Bonferroni correction. Results: The positive rates of bacterial culture in wound exudate of patients in PRP+ VSD on 7 and 14 d after the first treatment were 37.2% (16/43) and 11.6% (5/43), which were significantly lower than 56.8% (25/44) and 29.5% (13/44) in VSD alone group, χ(2)=4.212, 4.255, P<0.05. The wound healing rates of patients in PRP+ VSD group on 7 and 14, and 21 d after the first treatment were respectively (58±14)%, (70±13)%, (89±12)%, which were significantly higher than (41±11)%, (60±11)%, (74±12)% in VSD alone group, t=6.323, 3.820, 5.751, P<0.01. The complete wound healing time of patients in PRP+ VSD group was (30±6) d, which was significantly shorter than (61±8) d in VSD alone group, t=20.890, P<0.05. The VAS score of patients in PRP+ VSD group was significantly lower than that in VSD alone group on 14 d after the first treatment (t=13.904, P<0.01). The VSS score of patients in PRP+ VSD group was significantly lower than that in VSD alone group in 1 and 2 months after the wound healed completely (t=3.307, 3.637, P<0.01). The incidence of adverse reactions of patients in PRP+ VSD group during the whole period of treatment was 7.0% (3/43), which was significantly lower than 22.7% (10/44) in VSD alone group, χ(2)=4.245, P<0.05. Conclusions: Autologous PRP gel combined with VSD technology in repairing refractory wounds not only has good bacteriostatic effect, but also can increase wound healing rate, shorten wound healing time, alleviate wound pain, reduce scar hyperplasia, with less adverse reaction, which is worthy of promotion.

Peri-prostatic adipose tissue measurements using MRI predict prostate cancer aggressiveness in men undergoing radical prostatectomy.

OBJECTIVES: To evaluate the effect of peri-prostatic adipose tissue (PPAT) measurements using preoperative MRI on the prediction of prostate cancer (PCa) aggressiveness in men undergoing radical prostatectomy (RP). METHODS: We performed a retrospective study on 179 consecutive patients receiving RP from June 2016 to October 2018. Clinical characteristics were collected. PPAT measurements including peri-prostatic fat area (PPFA) and peri-prostatic fat area to prostate area (PA) ratio (PPFA/PA) were calculated by MRI. Multivariable logistic regression analysis was performed to identify independent predictors of PCa lymph node metastasis (LNM). The predictive performance was estimated through ROC curves. Nomograms were created based on the predictors. RESULTS: Pathologic Gleason score positively correlated with digital rectal examination (DRE), PSA, PPFA/PA, P504S, and Ki-67 (all P < 0.05). ROC curves revealed that high PPFA and high PPFA/PA were associated with LNM (both P < 0.05). Multivariate analysis revealed that high PPFA/PA, pathologic Gleason score, pT stage, and Ki-67 were independently predictive of LNM. The nomograms were created and the C-index was 0.945. CONCLUSIONS: PPFA/PA is an independent predictor for LNM along with Gleason score, pT stage, and Ki-67. PPFA/PA may help predict LNM in men undergoing RP, thus providing adjunctive information for therapeutic strategy and prognosis.

The morphological and physiological basis of delayed pollination overcoming pre-fertilization cross-incompatibility in Nicotiana.

Delayed pollination is widely used to overcome pre-fertilization incompatibility, but its regulatory mechanisms are unclear. When Nicotiana tabacum was cross-pollinated with pollen of N. alata, the incompatibility occurring in the basal 1/4 region of the style (pollinated at anthesis: 0-day-old pistil) was overcome by delayed pollination (of 6-day-old pistil), and the morphological changes and corresponding physiological basis are explored here. The structure and ultrastructure of the pistil were observed under fluorescence microscopy and transmission electron microscopy. Differentially expressed proteins were screened with a monoclonal antibody chip for Nicotiana, and protein expression and distribution were analysed by immunofluorescence. Cellulase and pectinase activities were tested using enzyme-linked immunosorbent assay kits. The style of Nicotiana is solid in the basal region and pollen tubes grow in the extracellular spaces (ECM) of the transmitting tissue (TTS) cells. Seven of the 22 identified proteins were cell wall-associated proteins and were expressed at higher levels during pistil senescence. Cellulase and pectinase activities increased. The TTS cells in the basal 1/4 region of the 0-day-old style were polygonal and tightly arranged, with narrow ECM, but these were oval or partially dissolved in the 6-day-old pistil, leading to wider ECM and richer secretions. The increased expression of cell wall proteins and enhanced enzyme activity during pistil senescence might partially be responsible for the cells becoming oval and the ECM enlarged, providing the morphological basis for delayed pollination overcoming the pre-fertilization incompatibility between N. tabacum and N. alata.

[Effect of free medial plantar perforator flap in repairing deep burn wound on palm with the assistance of three dimensional computed tomography angiography].

Objective: To explore the effect of free medial plantar perforator flap in repairing deep burn wound on palm with assistance of three dimensional computed tomography angiography (CTA). Methods: From March 2015 to January 2018, 11 patients with deep burn wounds of palm were admitted to the Department of Burns and Plastic Surgery of Yidu Central Hospital of Weifang City, including 6 males and 5 females, aged 19-53 years. The wound area after debridement was 3.0 cm×2.5 cm-8.0 cm×6.0 cm. Before the operation, CTA of the foot was performed, and the three dimensional digital model was reconstructed by computer software to observe the initial position, course, and distribution of the arteries and veins in the donor site. The medial plantar perforator flap was designed according to the area and shape of the wound, with area of 3.5 cm×3.0 cm-8.5 cm×6.5 cm. After the wound was covered by the flap, the perforating branch of the medial plantar artery was anastomosed end to end with the carpal epithelial branch of the ulnar artery, the accompanying vein or the branch of the great saphenous vein was anastomosed end to end with the accompanying vein of the carpal epithelial branch of the ulnar artery, and the terminal branch of the saphenous nerve or the medial dorsal cutaneous nerve was anastomosed end to end with the superficial palmar branch of the ulnar nerve. The wound of donor site was covered with full-thickness skin graft from the outer thigh of the same side. The perforators of the medial plantar artery observed during the operation were compared with the reconstructed three dimensional CTA images. The survival of flap was observed, and the appearance and function of the flap were followed up and evaluated with trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. Results: The initial position, course, and distribution of the perforator of the medial plantar artery during the operation were basically the same as those of the reconstructed three dimensional CTA images before the operation. All the flaps of patients survived after the operation. During the 6 months to 1 year follow-up, the appearance of flap was good, with no obvious swelling or pigmentation, but with good elasticity. The discrimination distance between the two points was 5.0-8.0 mm, and the flaps were evaluated as excellent in 4 cases, good in 6 cases, and fair in 1 case. Conclusions: The free medial plantar perforator flap is an ideal choice for repair of the deep burn wound on palm. Three dimensional CTA before the operation can detect condition of vascular variation, with high accuracy of vascular anastomosis during operation.

[Surgical treatment for type Stanford A aortic dissection with Kommerell's diverticulum].

Objective: To examine the outcomes of surgical treatment in patients of type Stanford A aortic dissection with Kommerell's diverticulum. Methods: From January 2009 to August 2017, patients of type Stanford A aortic dissection with Kommerell's diverticulum who underwent the Sun procedure were enrolled. Patient demographic, preoperative, intraoperative, early morbidity and mortality data were collected from medical and electronic patient records. Clinical follow-up data, including late morbidity and mortality, were obtained by telephone interview with the patient. Results: A total of 13 patients (11 males and 2 females; mean age 47 years) were included. The mean maximum diameter of Kommerell's diverticulum was (21.8±7.7) mm. The Kommerell's diverticulum was repaired by direct suture of the orifice in 3 patients, ligation of the aberrant right subclavian artery in 9 patients, and suture and ligation in 1 patient, respectively. No perioperative death occurred. One patient underwent a reexploration for bleeding. There were 2 late deaths: unknown reason in 1 patient and septic shock secondary to renal abscess in 1 patient. Reintervention was performed in one patient for a persistent type Ⅱ endoleak. Conclusions: The Sun procedure with femoral artery cannulation for cardiopulmonary bypass, unilateral carotid artery cannulation for selective cerebral perfusion and ligation of aberrant right subclavian artery on the right side of the trachea is an appropriate therapeutic strategy for patients of type Stanford A aortic dissection with Kommerell's diverticulum.

Rapid selection of analytical lines for SAF-LIBS based on the doublet intensity ratios at the initial and final stages of plasma.

Self-absorption-free laser-induced breakdown spectroscopy (SAF-LIBS) can directly obtain the applicable quasi-optically thin lines by determining the optimal acquisition delay time according to the intensity ratio of doublet lines at specific transition wavelength of the analyzed elements, thus eliminating the influence of self-absorption on quantitative results. In quantitative analysis of samples with a certain content range, the key to the convenient application of this technique is to rapidly select the suitable doublet lines for the element to be analyzed. The theoretical analysis shows that the evolution trend of doublet intensity ratio is monotonous under the assumptions that the plasma is uniform and in local thermal equilibrium (LTE) and the area density (Nl) is a constant, which is also confirmed by the experimental results of Cu and Al. Thus, a rapid spectral line selection criterion for SAF-LIBS applications is derived: only when the doublet intensity ratios measured at the initial and final stages of plasma induced by the boundary sample with the highest element content lie on both sides of the theoretical ratio, the doublet lines can reach quasi-optically thin during plasma evolution and are suitable for SAF-LIBS measurements. This new criterion is helpful to promote the practicality and industrial application of SAF-LIBS technology.

[Large clinical registries for acute aortic dissection: interpretation and comparison of latest results].

Despite the improvements in the diagnosis and management during the past six decades, acute aortic dissection (AAD) remains a life-threatening condition associated with significant morbidity and mortality rates. Due to the relatively rare occurrence of AAD, several clinical registries have been established to gain insights into this lethal disease in a large number of patients, such as the International Registry of Acute Aortic Dissection (IRAD), the German Registry for Acute Aortic Dissection Type A (GERAADA), and the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database Aortic Section. This review aims to interpret and compare the latest results of the IRAD, STS and GERAADA database. It focuses on several controversial and key issues in the diagnosis and management of acute aortic dissection in hope of providing some insights and references for cardiovascular professionals engaged in the care of this deadly disease.

Resonance/non-resonance doublet-based self-absorption-free LIBS for quantitative analysis with a wide measurement range.

A resonance/non-resonance, doublet-based, self-absorption-free, laser-induced breakdown spectroscopy (SAF-LIBS) technique is proposed for greatly expanding the measurement range of quantitative elemental analysis by using a quasi-optically thin line. The quasi-optically thin spectral line is obtained by matching the measured doublet atomic lines' intensity ratios with the theoretical one, and the applicable measurement range is expanded by utilizing the resonance and non-resonance lines. The specific calibration process consists of two parts: the nonlinear LIBS calibration and the linear SAF-LIBS calibration. For quantitative measurements, the approximate content of the unknown sample is determined first by using the LIBS calibration curve, and then the SAF-LIBS spectra and the resonance or non-resonance calibration curve that corresponds to the predetermined content are used for further implementing the quantitative analysis. Univariate quantitative analysis results of Cu show that this resonance/non-resonance doublet-based SAF-LIBS technique not only captures the quasi-optically thin spectral line in a wide range of elemental content, but also possesses high correlation coefficients of calibration curves, small relative errors of measurement and low limits of detection. The applicability and limitations of this technique are also discussed, and the evolution as well as the related major determinants of self-absorption are analyzed by taking advantage of the spatial-temporal evolution images of plasma emissivity.

[Renal mucinous tubular and spindle cell carcinoma combined with multiple bone metastasis: a case report and literature review].

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare sub-type of renal cell carcinoma (RCC). It has been considered to be a kind of "indolent" tumor with low-grade fashion, weak invasive capacity and relatively favorable prognosis. However, in the current case, a 3.7 cm×2.8 cm spherical mass with contrast enhancement was found in the left kidney incidentally by computed tomography (CT) in a 60-year-old male patient. A lesion in the right humerus (2.1 cm×1.6 cm×3.1 cm) was found at the same time without any symptoms or sign of pathological fracture by magnetic resonance (MR) imaging. Further positron emission tomography (PET)/CT scan which was ordered immediately after admission suggested multiple bone destruction including skull, pelvis, sternum, right humerus and femur, left scapula, multiple vertebrae and libs. Pathological examination after radical nephrectomy and palliative resection with internal fixation of the lesion in the right humerus indicated that both renal (3.0 cm×3.0 cm×2.5 cm) and bone lesions were MTSCC with the features of high-grade ovoid epithelioid cells, cord-like spindle cells and mucinous matrix under light microscope. The diagnosis of renal MTSCC concurrent with multiple bone metastasis was made. This case report suggested the necessity of general evaluation, especially bone scan for possible distant metastasis, as MTSCC might present unexpected advanced behaviors without any orthopedic symptoms. The behavior of bone metastasis might be associated with male and elderly age. MTSCC has similar enhancement features to papillary RCC on CT scan. As results, attentions are needed to differentiate MTSCC from papillary RCC as they both tend to show lesser enhancement degrees than cortex. Rather than exhibiting a dedifferentiating appearance, the pathological characteristics of bone metastasis lesion were close to those of primary renal lesion. The reason of distant metastasis to the bone remained unclear, negative expression of cytokeratin (CK) 7 might be attributed to. Though immunotherapy, chemotherapy and target therapy could all be methods for systematic therapies, procedures to remove renal lesions and prevent skeletal related events are still highly recommended.

Sequence analysis of peste des petits ruminants virus from ibexes in Xinjiang, China.

Peste des petits ruminants (PPR) is an infectious disease caused by peste des petits ruminants virus (PPRV). While PPR mainly affects domestic goats and sheep, it also affects wild ungulates such as ibex, blue sheep, and gazelle, although there are few reports regarding PPRV infection in wild animals. Between January 2015 and February 2015, it was found for the first time that wild ibexes died from PPRV infection in Bazhou, Xinjiang, China, where a total of 38 ibexes (including young and adult ibexes) were found to have died abnormally from PPR-related issues. First, we tested for the presence of the F gene of PPRV by RT-PCR. Then, we compared the sequence of the isolated F gene from the ibex strain, termed PPRV Xinjiang/Ibex/2015, with those previously identified from small domestic ruminants from local areas near where the reported isolate was collected as well as those from other regions. The current sequence was phylogenetically classified as a lineage IV virus, and shared a high level of sequence identity (99.7%) with a previously described Xinjiang PPRV isolate.

Valve-sparing operation for aortic root aneurysm in patients with Marfan syndrome.

BACKGROUND: We report our experience with aortic valve-sparing procedures in patients with Marfan syndrome and aortic root aneurysm. METHODS: Between August 2003 and July 2007, we performed aortic valve-sparing procedures in 20 patients with aortic root aneurysm resulting from Marfan syndrome. Mean age was 28 +/- 10 years (range, 10 to 57 years), and there were 9 females and 11 males. A reimplantation technique was used in 9 cases, a remodeling technique in 8 and a patch technique in 3 cases. Additional procedures included total aorta replacement in 1 patient, and aortic arch replacement plus stented elephant trunk in 2 patients. The mean follow-up time was 46 +/- 16 months (range, 17 to 64 months). RESULTS: No in-hospital or late death occurred. Reexploration for bleeding was required in one case on postoperative day 1. No valve-related complications occurred during the follow-up period. At the end of follow-up, trivial or no aortic regurgitation was demonstrated in 14 patients, mild in 4 patients, moderate in 1 and severe in 1. Two patients with moderate and severe aortic regurgitation required reoperation. CONCLUSIONS: The early and mid-term results of the valve-sparing operations were favorable, and the durability of the preserved valve should encourage use of this technique in patients with Marfan syndrome.

Neuroprotective effect of deep hypothermic circulatory arrest with low priming volume: study in a rabbit model.

OBJECTIVE: The aim of the study was to investigate the possible neuroprotective effects of a low priming volume following deep hypothermic circulatory arrest (DHCA) in a rabbit model. METHODS: Rabbits were randomized into three groups: DHCA with low priming volume (Group L), DHCA with high priming volume (Group H), and sham-operated group (Group S). The priming volume of Groups L and H were 75 ml and 210 ml, respectively. The rabbits were simultaneously placed on CPB and brain microdialysis, cooled to 16 to 18 degrees C with DHCA for 60 minutes. Physiological parameters were regularly recorded. The extracellular levels of glutamate, glucose, lactate, and pyruvate in the hippocampus were collected by microdialysis and measured by HPLC and a microdialysis analyzer. Brain damage was evaluated with light microscopy and electron microscopy and TUNEL staining. RESULTS: In order to keep the mean arterial pressure and acid-base balance within defined physiological ranges, more doses of dopamine and sodium bicarbonate were administered in Group H than in Group L (P < 0.05). The ratios of lactate/glucose and lactate/pyruvate in Group H increased significantly compared with those in Group L from the beginning of weaning from CPB (P < 0.05). The levels of extracellular glutamate in the two DHCA groups increased significantly (P < 0.05). After weaning from CPB, the glutamate values in Group H remained at higher levels compared with those in Group L (P < 0.05). The percentage of injured neurons, TUNEL positive staining, and the mitochondria score of the hippocampus CA1 in Group H were significantly higher than in Group L (P < 0.05). CONCLUSIONS: A low priming volume during DHCA could have a neuroprotective effect compared with a high priming volume.

Comparative analysis of pharmacologic and/or genetic disruption of cyclooxygenase-1 and cyclooxygenase-2 function in female reproduction in mice.

Cyclooxygenase (COX)-derived prostaglandins are critical in female reproduction. Gene targeting studies show that ovulation, fertilization, implantation, and decidualization are defective in COX-2 deficient mice. We used genetic and pharmacologic approaches to perturb COX function and examine the differential and synergistic effects of inhibition of COX-1, COX-2, or of both isoforms on reproductive outcomes during early pregnancy in mice. The results demonstrate that simultaneous inhibition of COX-1 and COX-2 produces more severe effects on early pregnancy events than inhibition of either isoform alone. The effects of pharmacological inhibition of COX-2 on female reproductive functions were less severe than the null mutation of the COX-2 gene. A combined approach showed that COX-2 inhibition in COX-1(-/-) mice induced complete reproductive failure, suggesting a lack of alternative sources of prostaglandin synthesis. This investigation raises caution regarding the indiscriminate use of COX inhibitors and shows for the first time the distinct and overlapping pathways of the cyclooxygenase systems in female reproduction.

Development of a new left ventricular assist device: the dynamic aortic valve.

We have been developing a new left ventricular assist device, an axial flow pump implanted at the aortic valve position. Since the device is intended for long-term use, its motor unit and pump are physically separated. The device consists of a "rotor-impeller" and a support cage. The rotor joins the impeller at one end and provides torque needed to spin the impeller. The support cage consists of a cantilever, a cantilever shaft, a top ring, and an end ring. The support cage is designed to fit within the ascending aorta and sutured to the aortic annulus during implantation. The magnetic rotor will rotate in the presence of alternating magnetic fields generated by an electric motor. The assembly also serves as a valve by maintaining the appropriate pressure drop across the aortic orifice. A prototype device was fabricated and tested in vitro. It produced a flow rate up to 5 L/min with a rotation rate of 12,600 rpm at a pressure difference of 100 mm Hg. The results proved the feasibility of the new device.

Implantation and decidualization defects in prolactin receptor (PRLR)-deficient mice are mediated by ovarian but not uterine PRLR.

PRL and its homologs accomplish their biological effects through the PRL receptor (PRLR). We evaluated the expression and function of PRLR in the embryo and uterus during the periimplantation period because PRLR deficiency results in implantation failure. In wild-type mice, PRLR expression was localized to undecidualized stromal cells in the antimesometrial border on days 6-8 of pregnancy. A small population of PRLR-expressing cells was observed adjacent to the ectoplacental cone in the mesometrial stroma. Low levels of PRLR expression were also detected in the developing embryo on days 6-8. To determine the significance of PRLR expression in this distribution, we examined implantation and decidualization in PRLR-/- mice. Progesterone (P4) administration rescued infertility in PRLR-/- mice from the periimplantation period to midgestation. Artificially induced decidualization was absent in pseudopregnant PRLR-/- mice but was identical to wild-type in P4-treated PRLR-/- mice. Furthermore, wild-type and P4-treated PRLR-/- mice had similar expression of the implantation-specific genes, LIF, amphiregulin, HB-EGF, COX-1, COX-2, PPARdelta, Hoxa-10, cyclin-D3, VEGF, and its receptors, Flk-1 and neuropilin-1. Together, these results show that luteal P4 production via ovarian PRLR signaling is required for implantation and early pregnancy. The function of uterine PRLR remains unclear. However, the eventual loss of pregnancy in P4-treated PRLR-/- mice suggests that uterine PRLR may be essential for the support of late gestation.

Fungitoxic alkaloids from Hokkaido Papaveraceae.

Papaver orientale, Dicentra spectabilis and Chelidonium majus, three Papaveraceae collected from Hokkaido area, were studied for their fungitoxic alkaloids. Ten alkaloids were isolated, identified and tested for their fungitoxic activity. Two of these isolates were found to be new compounds.

Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta.

We have demonstrated previously that cyclo-oxygenase-2 (COX2), the rate-limiting enzyme in the biosynthesis of prostaglandins (PGs), is essential for blastocyst implantation and decidualization. However, the candidate PG(s) that participates in these processes and the mechanism of its action remain undefined. Using COX2-deficient mice and multiple approaches, we demonstrate herein that COX2-derived prostacyclin (PGI2) is the primary PG that is essential for implantation and decidualization. Several lines of evidence suggest that the effects of PGI2 are mediated by its activation of the nuclear hormone receptor PPARdelta, demonstrating the first reported biologic function of this receptor signaling pathway.

Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse.

Hoxa-10 is an AbdominalB-like homeobox gene that is expressed in the developing genitourinary tract during embryogenesis and in the adult uterus during early pregnancy. Null mutation of Hoxa-10 in the mouse causes both male and female infertility. Defective implantation and decidualization resulting from the loss of maternal Hoxa-10 function in uterine stromal cells is the cause of female infertility. However, the mechanisms by which Hoxa-10 regulates these uterine events are unknown. We have identified two potential mechanisms for these uterine defects in Hoxa-10(-/-) mice. First, two PGE2 receptor subtypes, EP3 and EP4, are aberrantly expressed in the uterine stroma in Hoxa-10(-/-) mice, while expression of several other genes in the stroma (TIMP-2, MMP-2, ER, and PR) and epithelium (LIF, HB-EGF, Ar, and COX-1) are unaffected before implantation. Further, EP3 and EP4 are inappropriately regulated by progesterone (P4) in the absence of Hoxa-10, while PR, Hoxa-11 and c-myc, three other P4-responsive genes respond normally. These results suggest that Hoxa-10 specifically mediates P4 regulation of EP3 and EP4 in the uterine stroma. Second, since Hox genes are implicated in local cell proliferation, we also examined steroid-responsive uterine cell proliferation in Hoxa-10(-/-) mice. Stromal cell proliferation in mutant mice in response to P4 and 17beta-estradiol (E2 was significantly reduced, while epithelial cell proliferation was normal in response to E2. These results suggest that stromal cell responsiveness to P4 with respect to cell proliferation is impaired in Hoxa-10(-/-) mice, and that Hoxa-10 is involved in mediating stromal cell proliferation. Collectively, these results suggest that Hoxa-10 mutation causes specific stromal cell defects that can lead to implantation and decidualization defects apparently without perturbing epithelial cell functions.

Analysis of lactobacillus products for phages and bacteriocins that inhibit vaginal lactobacilli.

OBJECTIVE: Bacterial vaginosis is associated with an unexplained loss of vaginal lactobacilli. Previously, we have identified certain vaginal lactobacilli-released phages that can inhibit in vitro other vaginal lactobacilli. However, there is no apparent route for phages to be transmitted among women. The purpose of this study was to identify whether certain Lactobacillus products commonly used by women release phages or bacteriocins that can inhibit vaginal lactobacilli. METHODS: From 26 Lactobacillus products (2 acidophilus milks, 20 yogurts, 3 Lactobacillus pills, and 1 vaginal douche mix), lactobacilli were isolated with Rogosa SL agar (Difco, Detroit, MI). From these lactobacilli, phages and bacteriocins were induced with mitomycin C and tested against a collection of vaginal Lactobacillus strains. RESULTS: From the 26 products, 43 Lactobacillus strains were isolated. Strains from 11 yogurts released phages, among which 7 inhibited vaginal lactobacilli. Eleven strains released bacteriocins that inhibited vaginal lactobacilli. While about one-half of the vaginal strains were lysed by bacteriocins, less than 20% were lysed by phages. CONCLUSIONS: Some vaginal lactobacilli were inhibited in vitro by phages or bacteriocins released from Lactobacillus products used by women, implying that vaginal lactobacilli may be reduced naturally due to phages or bacteriocins from the environment.