Sirolimus inhibits platelet-derived growth factor-induced collagen synthesis in rat vascular smooth muscle cells

Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix (ECM) accumulation play key roles in the development and the progression of vascular remodeling such as transplant arteriosclerosis and restenosis. The present study examined the effects of sirolimus (SRL) on platelet-derived growth factor (PDGF)-induced fibronectin secretion, collagen synthesis, and the related signaling pathways including reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPK) in rat VSMCs. Primary rat VSMCs were isolated from male Sprague-Dawley rats. Growth arrested, synchronized cells were treated with various concentrations of SRL before the addition of PDGF at 10 ng/mL. Proliferating cell nuclear antigen expression, fibronectin secretion, and the activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK were assessed by Western blot analysis, collagen synthesis by [(3)H]-proline incorporation, and cellular ROS by flow cytometry. PDGF (10 ng/mL) increased VSMC proliferation by 1.7-fold, fibronectin secretion by 1.5-fold, collagen synthesis by 2.1-fold, cellular ROS by 1.6-fold, and activation of ERK and p38 MAPK by 3.3- and 3.9-fold compared to controls. SRL above 1 nmol/L inhibited PDGF-induced VSMC proliferation and collagen synthesis but not PDGF-induced fibronectin secretion, cellular ROS, and activation of ERK and p38 MAPK. These data demonstrated that PDGF increased ECM synthesis as well as proliferation through cellular ROS and subsequent MAPK activation and that SRL inhibited PDGF-induced VSMC proliferation and collagen synthesis in a cellular ROS- and MAPK activation-independent way.     

Lipid Levels: A Link Between Cardiovascular Disease and Osteoporosis?

Epidemiological observations support a positive relationship between cardiovascular diseases (CVD) and osteoporosis, where cholesterol has been indicated to be a possible link. Only a few studies have investigated the relation between lipids and BMD, but the association remains unclear. We studied the relationship between serum lipids and BMD of the calcaneus. A cross‐sectional population‐based study was performed, based on data from the Longitudinal Aging Study Amsterdam, including 620 men and 635 women, 65–88 yr of age. BMD was measured by quantitative ultrasound (QUS), velocity of sound (VOS; m/s), and broadband ultrasound attenuation (BUA; dB/MHz). Models were adjusted for age, body mass index, physical activity, smoking, alcohol, diabetes mellitus, hypertension, testosterone, and 25‐hydroxyvitamin D. No association was found between total cholesterol (TC) and QUS. Men and women in the highest quartile of high‐density lipoprotein cholesterol (HDL‐c) had a significantly lower QUS (men—VOS: β = ?20.8, p = 0.00; BUA: β = ?5.2, p = 0.02; women—VOS: β = ?18.6, p = 0.00) compared with men and women in the lowest quartile. An even stronger positive association was seen between TC/HDL‐c ratio and QUS (men—VOS: β = 21.8, p = 0.00; BUA: β = 5.5, p = 0.01; women—VOS: β = 19.2, p = 0.00; BUA: β = 3.6, p = 0.05). Our analysis shows that the lipid profile that is favorable in the prevention of CVD (i.e., high levels of HDL‐c and low TC/HDL‐c ratio) is unfavorable for QUS. These results indicate that HDL‐c levels do not explain the association between osteoporosis and CVD.     

What is the definition of “conversion” in laparoscopic colorectal surgery?

Background

A web-based survey was conducted among colorectal surgeons who represented members of both SAGES and ASCRS to find out how they define conversion for laparoscopic colorectal surgery.

Methods

Questionnaires were designed based on MCQs, including three parts: surgeon information, different definitions for conversion, and four different clinical scenarios. Surgeons were asked to choose the best definition(s).

Results

325 (28.5%) of 1,140 surgeons, 28.5% responded; approximately half of them were part of private-based practices. Fifty-three percent had more than 10 years experience; 35.9% performed more than 50 laparoscopic colon cases per year, 12% performed more than 25 laparoscopic rectal cases per year, and 60% less than 10. The majority (68.4%) agreed that any incision made earlier than planned is conversion. Whereas 81.4% felt that incision >5 cm is not a conversion, only 53.4% considered incision >10 cm a conversion, and 37% did not. Neither extracorporeal vessel ligation (73.8%), bowel resection (81.2%), anastomosis (77%), or incision made for specimen retrieval (91.1%) was counted as conversion. In clinical case scenarios, 62% found an incision made to facilitate phlegmon dissection after laparoscopically mobilizing the left colon up to and around the splenic flexure to be laparoscopic-assisted. A 10-cm incision required for fistula take down after finishing laparoscopic dissection was defined as conversion (55.6%). A 10-cm incision made for the rectal dissection in rectopexy was described as conversion in 51% and laparoscopic-assisted in 48%. Increasing a 5–12-cm for specimen extraction, 49.3% was declared a laparoscopic-assisted case.

Conclusions

It was considered clear that any incision made earlier than planned a conversion, whereas extra corporeal vessel ligation, bowel resection and anastomosis were not. However, there seem to be many views of conversion regarding incision length, and some clinical situations that might influence outcome among different centers.     

The 7‐year outcome of the tension‐free vaginal tape procedure for treating female stress urinary incontinence

OBJECTIVE

To evaluate the long‐term results and predictive risk factors for efficacy after the tension‐free vaginal tape (TVT) procedure for treating female stress urinary incontinence (SUI).

PATIENTS AND METHODS

Inall, 306 women (mean age 50.7 years, sd 8.7) who had a TVT procedure for SUI were selected and followed ≥7 years (mean 92.3 months, range 84–110) after surgery. We analysed the long‐term results, the variables predictive of cure rates, and patient satisfaction.

RESULTS

The overall 7‐year cure rate was 84.6%, with a satisfaction rate of 69.3%. The cure rates were lower in patients with high‐grade SUI (50% in grade III, 82.8% in grade II and 90.7% in grade I; P < 0.001). On multivariate analysis, there were no independent risk factors related to cure rate, and urgency was the only factor independently associated with patient satisfaction (P = 0.008; odds ratio 2.47). Seventy‐one patients (23.2%) had complications at the 1‐month follow‐up after surgery, but only eight (2.6%) had complications at the 7‐year follow‐up, including mesh exposure in six and de novo urgency in two.

CONCLUSION

The absence of long‐term adverse events associated with the TVT procedure, and high subjective and objective 7‐year success rates with no independent predictive factors affecting the long‐term cure rate, make the TVT procedure a recommendable surgical treatment for female SUI.     

Abdominal wall recurrence of Hilar bile duct cancer 12 years after a curative resection: Report of a case

A 74-year-old woman was diagnosed with hilar bile duct cancer, and underwent a curative resection of the bile duct and the left and caudate lobes of the liver in 1995. Ten years later (April 2005), she noted a small mass in the abdominal wall. The mass slowly enlarged to reach 4 cm in diameter by January 2007. With a diagnosis of a possible recurrence of bile duct cancer, a laparotomy was thus performed. The abdominal wall tumor was buried in the rectus abdominis muscle and was tightly attached to the ileum. The lesion was resected en bloc with the associated rectus muscle and ileocecal region. A histopathological examination of the resected specimen revealed tubular adenocarcinoma that closely resembled the original primary bile duct cancer. In addition, the immunohistochemical staining pattern of the abdominal tumor was identical to that of the original bile duct cancer. This indicated that the abdominal tumor represented a local recurrence (probably due to peritoneal implantation) at 12 years after the resection of the hilar bile duct cancer. This case emphasizes that long-time surveillance is required for patients with bile duct cancer, even if they have survived without recurrence for more than 5 years after a curative resection.     

Expression of cubilin in mouse testes and Leydig cells

Cubilin (cubn) is a receptor for vitamins and various protein ligands. Cubn lacks a transmembrane domain but anchors to apical membranes by forming complexes with Amnionless or Megalin. In an effort to better understand the uptake of nutrients in testis, we analysed cubn expression in the developing mice testes. In testes, cubn mRNA increased from birth to adulthood. In the inter‐stitium and isolated seminiferous tubules, neonatal increase in cubn mRNA until 14 days post‐partum (pp) was followed by a marked increase at puberty (28 days pp). Cubn was found in the gonocytes, spermatogonia, spermatocytes and spermatids in the developing testes. In adult testes, strong Cubn immunoreactivity was found in the elongating spermatids, suggesting the role of Cubn in endocytosis during early spermiogenesis. In Sertoli cells and peritubular cells, Cubn immunoreactivity was weak throughout the testis development. In the inter‐stitium, Cubn immunoreactivity was found in foetal Leydig cells, was weak to negligible in the stem cells and progenitor Leydig cells and was strong in immature and adult Leydig cells, demonstrating a positive association between Cubn and steroidogenic activity of Leydig cells. Collectively, these results suggest that Cubn may participate in the endocytotic uptake of nutrients in germ cells and somatic cells, supporting the spermatogenesis and steroidogenesis in mouse testes.     

The effects of human keratinocyte coculture on human adipose‐derived stem cells

The potential for adipose‐derived stem cells to differentiate into keratinocyte‐like cells has recently been receiving attention, stemming from the hypothesis that a bioengineered skin may be manufactured from these readily available mesenchymal stem cells. This study was conducted to evaluate the influence of human keratinocyte non‐contact coculture on hADSCs. Human epidermal keratinocytes and hADSCs obtained by lipoaspiration were cultured in keratinogenic growth media, which were divided into the following groups: human adipose‐derived stem cell (hADSC) monoculture, non‐contact coculture of hADSCs and human keratinocytes and keratinocyte monoculture. Cell proliferation was assessed, and keratogenicity was analysed through immunocytochemistry and polymerase chain reaction of early, intermediate and late keratogenic markers. hADSCs cocultured with keratinocytes displayed enhanced proliferation compared with the monoculture group. After a 7‐day coculture period, immunohistochemistry and polymerase chain reaction findings revealed the presence of specific keratinocyte markers in the coculture group. This study demonstrates that hADSCs cocultured with keratinocytes have the capacity to transdifferentiate into keratinocyte lineage cells, and suggests that adipose tissue may be a source of keratinocytes that may further be used in structuring the bioengineered skin.     

Use of the airway scope for difficult airway

The Airway Scope (AWS) is a new videolaryngoscope which consists of an optical system and a single-use blade. The blade of the device is designed according with the pharyngeal anatomy, and thus the AWS is expected to have a role in the management of difficult airway. We here report 15 patients with difficult airway in whom the AWS provided in successful intubation. The AWS provides a view of the glottis with Cormack-Lehane grade 1 and resulted in successful intubation in the 15 patients. The AWS is useful for the management of difficult airway.     

The effect of overactive bladder syndrome on the sexual quality of life in Korean young and middle aged women

Some reports showed that urinary incontinence (UI) or female lower urinary tract symptoms (LUTS) affect life quality and sexual activity. In clinical practice, it is commonly found that not only the symptoms of UI but also overactive bladder (OAB) syndrome affect daily lifestyle and sexual activity, especially in women in the most active era in their social and personal life. However, there is lack of data proving the effect of OAB syndrome on sexual activity or sexual life quality in sexually active age group. This study aimed at evaluating the effect of OAB syndrome and UI on the sexual activity and on the sexual quality of life (QoL) of Korean women age from 20s to 40s. We investigated 3372 women aged between 20 and 49 y, enrolled via a multicenter internet survey. A structured questionnaire was used to collect data about their LUTS and sexual activities. The prevalence of OAB syndrome and UI in 3372 women was 12.7 and 21.0%, respectively. Mean subject age was 26.4+/-4.8 y and 79.5% of subjects were 20-29 y old. Having OAB syndrome or UI were found to be significant predictors of sexual life problems (OAB syndrome: OR=5.08, 95% CI=3.68-7.01; UI: OR=4.16, 95% CI=3.06-5.67). Sexual activity was significantly reduced in OAB syndrome and UI versus the asymptomatic group (OAB syndrome: OR=4.8, 95% CI=3.14-6.83; UI: OR=3.9, 95% CI=2.81-5.27). This study is the first internet-based study concerning the sexual QoL in UI and OAB syndrome. In this study, OAB syndrome was found to cause a greater deterioration in the sexual QoL than UI. These results suggest that these symptoms have a significant impact upon women's personal and social lives and markedly affect the QoL.