Chronic obstructive pulmonary disease (COPD) is a lung disease caused by an inflammatory response to various inhaled toxins, especially cigarette smoke. Reactive oxygen species (ROS) and epigenetic ...abnormality are intimately related to the pathology of COPD, and the overproduction of ROS results in a decrease of histone deacetylase 2 (HDAC2), leading to glucocorticoid resistance. Therefore, a novel treatment that simultaneously reduces ROS level and glucocorticoid resistance is urgently needed. In this study, we developed a codelivery system using core-shell type lipid-polymer nanoparticles (LPNs) composed of a poly(lactic acid) (PLA) core encapsulating a potent antioxidant Mn-porphyrin dimer (MnPD) and a cationic lipid (DOTAP) shell that binds HDAC2-encoding plasmid DNA (pHDAC2), as a new therapeutic approach toward COPD. The transfection of pHDAC2 combined with the elimination of ROS by MnPD exhibited a significant enhancement of intracellular HDAC2 expression levels, suggesting that the multi-antioxidative activity of MnPD plays a crucial role in the expression of HDAC2. Moreover, treatment with LPNs efficiently ameliorated the steroid resistance in COPD models in vitro as evidenced by the lowered expression levels of IL-8. Recovery from mitochondrial dysfunction may be the mechanism underlying the action of LPNs. The PLA-MnPD/DOTAP/pHDAC2 system proposed offers a new therapeutic approach for COPD based on the synergism of ROS elimination and HDAC2 expression.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Hypertension and osteoporosis are two major age‐related disorders; however, the underlying molecular mechanism for this comorbidity is not known. The renin‐angiotensin system (RAS) plays a central ...role in the control of blood pressure and has been an important target of antihypertensive drugs. Using a chimeric RAS model of transgenic THM (Tsukuba hypertensive mouse) expressing both the human renin and human angiotensinogen genes, we showed in this study that activation of RAS induces high turnover osteoporosis with accelerated bone resorption. Transgenic mice that express only the human renin gene were normotensive and yet exhibited a low bone mass, suggesting that osteoporosis occurs independently of the development of hypertension per se. Ex vivo cultures showed that angiotensin II (AngII) acted on osteoblasts and not directly on osteoclast precursor cells and increased osteoclastogenesis‐supporting cytokines, RANKL and vascular endothelial growth factor (VEGF), thereby stimulating the formation of osteoclasts. Knockdown of AT2 receptor inhibited the AngII activity, whereas silencing of the AT1 receptor paradoxically enhanced it, suggesting a functional interaction between the two AngII receptors on the osteoblastic cell surface. Finally, treatment of THM mice with an ACE inhibitor, enalapril, improved osteoporosis and hypertension, whereas treatment with losartan, an angiotensin receptor blockers specific for AT1, resulted in exacerbation of the low bone mass phenotype. Thus, blocking the synthesis of AngII may be an effective treatment of osteoporosis and hypertension, especially for those afflicted with both conditions.
Caloric restriction (CR) extends the lifespan of various organisms and slows the onset of age-related disorders; however, little is known about the long-term effects of CR per se on bone. In the ...present study, we have examined the effects of life-long CR vs. ad libitum (AD) feeding, mainly on the trabecular bone of proximal tibiae in male C57BL/6 mice and F344 rats. Micro-computed tomography scanning of tibiae revealed that CR for 3–9 months caused a substantial decrease in three-dimensional bone volume with structural derangements. Bone histomorphometry revealed the reduced bone mass was due mainly to suppression of bone formation. In db/db mice with defective leptin receptor, CR was unable to decrease bone mass and suppress bone formation. The effect of CR on bone mass was inhibited by administration of a β-adrenergic blocker, propranolol. Thus, CR may regulate bone formation through leptin signaling and elevated sympathetic nervous tone. Interestingly, the difference in bone volume between the CR and AD groups disappeared after 1 yr of age, and mice and rats on an additional extension of CR to natural death maintained higher bone mass than the AD groups, with reduced bone turnover, suggesting that CR slows skeletal aging by regulating the rate of bone turnover. This is the first report, to our knowledge, that has examined the effects of lifelong CR on bone metabolism and trabecular microstructure and documents its contrasting effects during maturation vs. the postmaturational, involutional period.
Although nasogastric tube (NGT) decompression is widely used in nonoperative management for adhesive small bowel obstruction (SBO), robust evidence is lacking to support this routine practice.
...Patients who received nonoperative management with a diagnosis of adhesive SBO were retrospectively reviewed. Those who received NGT or long-tube decompression at admission were categorized into the NGT group, while those who initially had no NGT placement were categorized into the non-NGT group. The incidence of vomiting after admission, pneumonia after admission, and the need for surgery were compared.
Among 288 patients, 148 (51.3%) had non-NGT conservative treatment. There were no significant differences in the incidence of vomiting (NGT vs non-NGT: 12.9% vs 18.9%, p = 0.16), pneumonia (1.4% vs 0%, p = 0.235), or need for surgery (12.9% vs 7.4%, p = 0.126).
While NGT decompression is a standard of care for adhesive SBO, selective NGT insertion for patients with persistent nausea or vomiting can become an option.
•Vomiting rate was low in nonoperative management without nasogastric tube.•Non-nasogastric tube decompression did not increase pneumonia and need for surgery.•Non-nasogastric tube decompression did not increase vomiting rate in patients with large gastric volumes.•Selective patients may avoid nasogastric tube insertion in nonoperative management.
Purpose
The long-term prognosis of stapled and hand-sewn ileal pouch–anal anastomoses in familial adenomatous polyposis patients in Japan remains unknown. This study aimed to compare the overall ...survival in familial adenomatous polyposis patients who underwent stapled or hand-sewn ileal pouch–anal anastomosis.
Methods
This multicenter retrospective study was conducted at 12 institutions in Shizuoka Prefecture, Japan. The clinical outcomes of 53 eligible familial adenomatous polyposis patients who underwent stapled (
n
= 24) and hand-sewn (
n
= 29) ileal pouch–anal anastomosis were compared.
Results
The median follow-up duration was 171.5 months. The incidence of adenoma in the remnant rectum or anal transitional zone and metachronous rectal cancer was significantly more common in stapled ileal pouch–anal anastomosis (adenoma: stapled, 45.8%, vs. hand-sewn, 10.3%,
p
= 0.005; metachronous rectal cancer: 29.2%, vs. none,
p
= 0.002). The number of deaths was remarkably higher in stapled ileal pouch–anal anastomosis (
p
= 0.002). Metachronous rectal cancer was the most common cause of death. Overall survival was worse in stapled ileal pouch–anal anastomosis than in hand-sewn ileal pouch–anal anastomosis (120 months, 90.7% vs. 96.6%; 240 months, 63.7% vs. 96.6%;
p
= 0.044). Cox regression analysis revealed the independent effects of preoperative advanced colorectal cancer and stapled ileal pouch–anal anastomosis on overall survival.
Conclusion
Stapled ileal pouch–anal anastomosis negatively affected the overall survival of familial adenomatous polyposis patients. Therefore, hand-sewn ileal pouch–anal anastomosis is recommended for better prognosis in these patients.
Radiation-associated Breast Angiosarcoma—A Case Report YONEKAWA, Yoshihiko; ASABA, Yutaro; MAETA, Takao ...
Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association),
2022, 2022-00-00, Letnik:
83, Številka:
7
Journal Article
Odprti dostop
The case involved a 76-year-old woman with a history of breast-conserving surgery 7 years ago. On the follow-up visit, she complained about a pigmented subcutaneous induration on her ipsilateral ...breast skin resembling chronic dermatitis. This was treated with a topical steroid ointment without any improvement for the next 2 months. Skin biopsy revealed angiosarcoma, and a CT scan showed a small subcutaneous mass with focal contrast-enhancement. The tumor showed a rapid-washout pattern on dynamic MRI. An FDG-PET CT scan showed marked accumulation of FDG (SUV-max 39.1) only at the tumor site. Therefore, the patient was diagnosed with radiation-associated breast angiosarcoma and underwent breast-conserving resection with pathological R0 resection. The patient has been disease free for the last 10 months with no additional treatment.Radiation-associated angiosarcoma is a rare condition that arises only in 0.1% of patients who have undergone breast-conserving surgery. A review of well-documented literature involving cases from the Japanese population revealed high local and distant recurrence rates after resection and a dismal five-year survival of 46%. This rare, but clinically significant, condition must be acknowledged before breast-conserving surgery is performed and radiation therapy is administered.
Abstract
An 81-year-old woman had undergone laparoscopic abdominoperineal resection for rectal cancer. A permanent colostomy was created through an intraperitoneal route. Three months after the ...surgery, the patient presented with lower abdominal pain and vomiting. Computed tomography showed gastric incarceration through the lateral space of the lifted sigmoid colostomy. Although the herniated stomach was reduced by nasogastric tube decompression, the patient experienced a recurrence of gastric hernia shortly thereafter. A laparoscopic operation was performed, and a new colostomy was constructed through an extraperitoneal route. The patient had no hernia recurrence during the 20 months of follow-up after the operation. Gastric internal hernia associated with colostomy can occur as a rare complication. Although reduction of the incarcerated stomach is possible by nasogastric tube decompression, surgical repair of the hernia may be the optimal management to prevent recurrence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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