Platelets modulate gastric ulcer healing: Role of endostatin and vascular endothelial growth factor release

Bleeding and delayed healing of ulcers are well recognized clinical problems associated with the use of aspirin and other nonsteroidal antiinflammatory drugs, which have been attributed to their antiaggregatory effects on platelets. We hypothesized that antiplatelet drugs might interfere with gastric ulcer healing by suppressing the release of growth factors, such as vascular endothelial growth factor (VEGF), from platelets. Gastric ulcers were induced in rats by serosal application of acetic acid. Daily oral treatment with vehicle, aspirin, or ticlopidine (an ADP receptor antagonist) was started 3 days later and continued for 1 week. Ulcer induction resulted in a significant increase in serum levels of VEGF and a significant decrease in serum levels of endostatin (an antiangiogenic factor). Although both aspirin and ticlopidine markedly suppressed platelet aggregation, only ticlopidine impaired gastric ulcer healing and angiogenesis as well as reversing the ulcer-associated changes in serum levels of VEGF and endostatin. The effects of ticlopidine on ulcer healing and angiogenesis were mimicked by immunodepletion of circulating platelets, and ticlopidine did not influence ulcer healing when given to thrombocytopenic rats. Incubation of human umbilical vein endothelial cells with serum from ticlopidine-treated rats significantly reduced proliferation and increased apoptosis, effects reversed by an antibody directed against endostatin. Ticlopidine treatment resulted in increased platelet endostatin content and release. These results demonstrate a previously unrecognized contribution of platelets to the regulation of gastric ulcer healing. Such effects likely are mediated through the release from platelets of endostatin and possibly VEGF. As shown with ticlopidine, drugs that influence gastric ulcer healing may do so in part through altering the ability of platelets to release growth factors.

Microglial Cells Prevent Hemorrhage in Neonatal Focal Arterial Stroke

Perinatal stroke leads to significant morbidity and long-term neurological and cognitive deficits. The pathophysiological mechanisms of brain damage depend on brain maturation at the time of stroke. To understand whether microglial cells limit injury after neonatal stroke by preserving neurovascular integrity, we subjected postnatal day 7 (P7) rats depleted of microglial cells, rats with inhibited microglial TGFbr2/ALK5 signaling, and corresponding controls, to transient middle cerebral artery occlusion (tMCAO). Microglial depletion by intracerebral injection of liposome-encapsulated clodronate at P5 significantly reduced vessel coverage and triggered hemorrhages in injured regions 24 h after tMCAO. Lack of microglia did not alter expression or intracellular redistribution of several tight junction proteins, did not affect degradation of collagen IV induced by the tMCAO, but altered cell types producing TGFβ1 and the phosphorylation and intracellular distribution of SMAD2/3. Selective inhibition of TGFbr2/ALK5 signaling in microglia via intracerebral liposome-encapsulated SB-431542 delivery triggered hemorrhages after tMCAO, demonstrating that TGFβ1/TGFbr2/ALK5 signaling in microglia protects from hemorrhages. Consistent with observations in neonatal rats, depletion of microglia before tMCAO in P9 Cx3cr1(GFP/+)/Ccr2(RFP/+) mice exacerbated injury and induced hemorrhages at 24 h. The effects were independent of infiltration of Ccr2(RFP/+) monocytes into injured regions. Cumulatively, in two species, we show that microglial cells protect neonatal brain from hemorrhage after acute ischemic stroke. SIGNIFICANCE STATEMENT The pathophysiological mechanisms of brain damage depend on brain maturation at the time of stroke. We assessed whether microglial cells preserve neurovascular integrity after neonatal stroke. In neonatal rats, microglial depletion or pharmacological inhibition of TGFbr2/ALK5 signaling in microglia triggered hemorrhages in injured regions. The effect was not associated with additional changes in expression or intracellular redistribution of several tight junction proteins or collagen IV degradation induced by stroke. Consistent with observations in neonatal rats, microglial depletion in neonatal mice exacerbated stroke injury and induced hemorrhages. The effects were independent of infiltration of monocytes into injured regions. Thus, microglia protect neonatal brain from ischemia-induced hemorrhages, and this effect is consistent across two species.

A treatise on the process employed by nature in suppressing the hemorrhage from divided and punctured arteries : and on the use of the ligature : concluding with observations on secondary hemorrhage, the whole deduced from an extensive series of experiments and illustrated by fifteen plates /

Mode of access: Internet.

A treatise on the process employed by nature in suppressing the hemorrhage from divided and punctured arteries, and on the use of the ligature; concluding with observations on secondary hemorrhage. The whole deduced from an extensive series of experiments ...

First published in London in 1805.

Hemorrhage and transfusion; an experimental and clinical research,

Bibliography: p. [537]-549.

Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region - An overview of 26 cohorts involving 306,620 participants

Background and Purpose - The cause of subarachnoid hemorrhage ( SAH) is poorly understood and there are few large cohort studies of risk factors for SAH. We investigated the risk of SAH mortality and morbidity associated with common cardiovascular risk factors in the Asia-Pacific region and examined whether the strengths of these associations were different in Asian and Australasian ( predominantly white) populations. Methods - Cohort studies were identified from Internet electronic databases, searches of proceedings of meetings, and personal communication. Hazard ratios (HRs) for systolic blood pressure (SBP), current smoking, total serum cholesterol, body mass index (BMI), and alcohol drinking were calculated from Cox models that were stratified by sex and cohort and adjusted for age at risk. Results - Individual participant data from 26 prospective cohort studies ( total number of participants 306 620) that reported incident cases of SAH ( fatal and/or nonfatal) were available for analysis. During the median follow-up period of 8.2 years, a total of 236 incident cases of SAH were observed. Current smoking (HR, 2.4; 95% CI, 1.8 to 3.4) and SBP > 140 mm Hg ( HR, 2.0; 95% CI, 1.5 to 2.7) were significant and independent risk factors for SAH. Attributable risks of SAH associated with current smoking and elevated SBP ( similar to 140 mm Hg) were 29% and 19%, respectively. There were no significant associations between the risk of SAH and cholesterol, BMI, or drinking alcohol. The strength of the associations of the common cardiovascular risk factors with the risk of SAH did not differ much between Asian and Australasian regions. Conclusions - Cigarette smoking and SBP are the most important risk factors for SAH in the Asia-Pacific region.

Translation and validation of the Chinese version of the Charing Cross Venous Ulcer Questionnaire

No Abstract

Pressure ulcers and nutritional deficits in elderly long-term care patients: Effects of a comprehensive nutritional program on pressure ulcer healing, length of hospital stay and charges to patients

The elderly are at the highest risk of developing pressure ulcers that result in prolonged hospitalization, high health care costs, increased mortality, and decreased quality of life. The burden of pressure ulcers will intensify because of a rapidly increasing elderly population in the United States (US). Poor nutrition is a major predictor of pressure ulcer formation. The purpose of this study was to examine the effects of a comprehensive, interdisciplinary nutritional protocol on: (1) pressure ulcer wound healing (2) length of hospital stays, and (3) charges for pressure ulcer management. Using a pre-intervention/post intervention quasi-experimental design the study sample was composed of 100 patients 60 years or older, admitted with or acquiring a pressure ulcer. A pre-intervention group (n= 50) received routine pressure ulcer care (standard diet, dressing changes, and equipment). A post-intervention group received routine care plus an interdisciplinary nutrition intervention (physical therapy, speech therapy, occupational therapy, added protein and calories to the diet). Research questions were analyzed using descriptive statistics, frequencies, Chi-Square Tests, and T-tests. Findings indicated that the comprehensive, interdisciplinary nutritional protocol had a significant effect on the rate of wound healing in Week3 and Week4, total hospital length of stay (pre-intervention M= 43.2 days, SD=31.70 versus M=31.77, SID-12.02 post-intervention), and pressure ulcer length of stay (pre-intervention 25.28 days, SD5.60 versus 18.40 days, SD 5.27 post-intervention). Although there was no significant difference in total charges for the pre-intervention group ($727,245.00) compared to the post-intervention group ($702,065.00), charges for speech (m=$5885.12, SD=$332.55), pre albumin (m=$808.52,SD= $332.55), and albumin($278 .88, SD=55.00) were higher in the pre-intervention group and charges for PT ($5721.26, SD$3655.24) and OT($2544 .64, SD=1712.863) were higher in the post-intervention group. Study findings indicate that this comprehensive nutritional intervention was effective in improving pressure ulcer wound healing, decreasing both hospital length of stay for treatment of pressure ulcer and total hospital length of stay while showing no significant additional charges for treatment of pressure ulcers.

Pressure ulcers and nutritional deficits in elderly long-term care patients : effects of a comprehensive nutritional program on pressure ulcer healing, length of hospital stay and charges to patients

The elderly are at the highest risk of developing pressure ulcers that result in prolonged hospitalization, high health care costs, increased mortality, and decreased quality of life. The burden of pressure ulcers will intensify because of a rapidly increasing elderly population in the United States (US). Poor nutrition is a major predictor of pressure ulcer formation. The purpose of this study was to examine the effects of a comprehensive, interdisciplinary nutritional protocol on: 1) pressure ulcer wound healing 2) length of hospital stays, and 3) charges for pressure ulcer management. Using a pre-intervention/post intervention quasi-experimental design the study sample was composed of 100 patients 60 years or older, admitted with or acquiring a pressure ulcer. A pre-intervention group (n= 50) received routine pressure ulcer care (standard diet, dressing changes, and equipment). A post-intervention group received routine care plus an interdisciplinary nutrition intervention (physical therapy, speech therapy, occupational therapy, added protein and calories to the diet). Research questions were analyzed using descriptive statistics, frequencies, Chi-Square Tests, and T-tests. Findings indicated that the comprehensive, interdisciplinary nutritional protocol had a significant effect on the rate of wound healing in Week3 and Week4, total hospital length of stay (pre-intervention M= 43.2 days, SD=31.70 versus M=31.77, SD=12.02 post-intervention), and pressure ulcer length of stay (pre-intervention 25.28 days, SD5.60 versus 18.40 days, SD 5.27 post-intervention). Although there was no significant difference in total charges for the pre-intervention group ($727,245.00) compared to the post-intervention group ($702,065.00), charges for speech (m=$5885.12, SD=$332.55), pre albumin (m=$808.52,SD= $332.55), and albumin($278 .88, SD=55.00) were higher in the pre-intervention group and charges for PT ($5721.26, SD$3655.24) and OT($2544 .64, SD=1712.863) were higher in the post-intervention group. Study findings indicate that this comprehensive nutritional intervention was effective in improving pressure ulcer wound healing, decreasing both hospital length of stay for treatment of pressure ulcer and total hospital length of stay while showing no significant additional charges for treatment of pressure ulcers.

The Barriers to the Integration of the Uterine Balloon Tamponade into South Africa and Ghana's Health Systems for the Management of Postpartum Hemorrhage

Background

Postpartum hemorrhage is the most significant contributor to maternal mortality globally, claiming 140,000 lives annually. Postpartum hemorrhage is a leading cause of maternal death in South Africa, with the literature indicating that 80 percent of the postpartum hemorrhage deaths in South Africa are avoidable. Ghana, as of 2010, witnesses 2700 maternal deaths annually, primarily because of poor quality of care in health facilities and services being difficult to access. As per WHO recommendations, uterotonics are integral to treating postpartum hemorrhage as soon as it is diagnosed. In case of persistent bleeding or limited availability of uterotonics, the uterine balloon tamponade (UBT) can be used as a second line of defense. If both these measures are unable to counter the bleeding, providers must perform surgical interventions. Literature on the UBT, as one tool in the protocol to address postpartum hemorrhage, has shown it to have success rates ranging from 60 to 100 percent. Despite the potential to lower the number of postpartum hemorrhage deaths in South Africa and Ghana, the UBT has not been incorporated widely in South Africa and Ghana. The aim of this study is to describe the barriers involved with integrating the UBT into South Africa and Ghana’s health systems to address postpartum hemorrhage.

Methods

The study took place in multiple sites in South Africa (Cape Town, Johannesburg, Durban and Mpumalanga) and in Accra, Ghana. South Africa and Ghana were selected because postpartum hemorrhage contributes greatly to their maternal mortality numbers and there is potential in both countries to lower those rates through greater use of the UBT. A total of 25 participants were interviewed through purposive sampling, snowball sampling and participant referrals, and included various categories of stakeholders integral to the integration process of a medical device. Individual in-depth interviews were used for data collection, with interview questions being tailored to each stakeholder category. The focus of the interviews was on the protocol used to counter postpartum hemorrhage, the frequency with which the UBT is used as part of the protocol, and the process of integrating it into the South Africa and Ghana’s health systems. The data collected were coded using NVivo and analyzed using content analysis.

Results

The barriers to integration of the uterine balloon tamponade to address postpartum hemorrhage in South Africa and Ghana were evident on the political, economic and health delivery levels. The results indicated that the barriers to integration in South Africa included the low recognition of postpartum hemorrhage as a problem, the lack of clarity surrounding the role of the Medicines Control Council as a regulatory body for medical devices, and low awareness of the UBT as an intervention to control postpartum hemorrhage. The barriers in Ghana were the cash constraints experienced by the Ghana Health Services to fund medical devices, a heavy reliance on donors for funding, and the lack of consistent knowledge on processes involving clinical trials for new medical devices in Ghana.

Conclusion

Existing literature on methods to counter postpartum hemorrhage to reduce maternal mortality has focused on and emphasized the efficacy of the UBT. Despite overwhelming evidence supporting the use of the UBT, many health systems across the world, particularly low-income countries, do not have access to the device owing to numerous barriers in integrating the device into obstetric care. This study illustrates the need to focus on incorporating the UBT into health systems for greater availability to health workers and its use as standard of care. Ultimately, this study can be used as a stepping-stone for more research on this subject, providing evidence to influence policymakers to integrate the UBT into their protocols for postpartum hemorrhage response.

Effects of Purified Saccharomyces cerevisiae (1→3)-β-Glucan on Venous Ulcer Healing

Water-insoluble glucan was isolated from the baker’s yeast Saccharomyces cerevisiae. The yeast cells were treated with alkali and the residue then with acid. Chemical and NMR (1D and 2D) analyses showed that a linear (1→3)-β-glucan was purified that was not contaminated with other carbohydrates, proteins or phenolic compounds. The effects of the glucan on wound healing were assessed in human venous ulcers by histopathological analysis after 30 days of topical treatment. (1→3)-β-glucan enhanced ulcer healing and increased epithelial hyperplasia, as well as increased inflammatory cells, angiogenesis and fibroblast proliferation. In one patient who had an ulcer that would not heal for over 15 years, glucan treatment caused a 67.8% decrease in the area of the ulcer. This is the first study to investigate the effects of (1→3)-β-glucan on venous ulcer healing in humans; our findings suggest that this glucan is a potential natural biological response modifier in wound healing

Effects of Purified Saccharomyces cerevisiae (1→3)-β-Glucan on Venous Ulcer Healing

Water-insoluble glucan was isolated from the baker’s yeast Saccharomyces cerevisiae. The yeast cells were treated with alkali and the residue then with acid. Chemical and NMR (1D and 2D) analyses showed that a linear (1→3)-β-glucan was purified that was not contaminated with other carbohydrates, proteins or phenolic compounds. The effects of the glucan on wound healing were assessed in human venous ulcers by histopathological analysis after 30 days of topical treatment. (1→3)-β-glucan enhanced ulcer healing and increased epithelial hyperplasia, as well as increased inflammatory cells, angiogenesis and fibroblast proliferation. In one patient who had an ulcer that would not heal for over 15 years, glucan treatment caused a 67.8% decrease in the area of the ulcer. This is the first study to investigate the effects of (1→3)-β-glucan on venous ulcer healing in humans; our findings suggest that this glucan is a potential natural biological response modifier in wound healing

Hyaluronic acid as neuropathic ulcer treatment: a case report

The prevalence of diabetic polyneuropathy in Spain is 22% increasing with age, standing at less than 5% in patients between 15 and 19 years and reaching 29.8% in those aged 70 to 74 years age. Infection is an important complication in Diabetic Foot, frequently associated with minor amputation and even lower extremity amputation. The study presents a clinical case of a 68-year-old man who consulted for a diabetic foot ulcer in the metatarseal area of the right foot, diagnosed two years ago and without healing success. An exploration protocol of the diabetic food was made. Afterwards, a surgical debridement was done and a cure procedure with pure hyaluronic acid, a bandage and foot unloading was followed. After 69 days of treatment, a complete ulcer healing was achieved. After the injure healing, a biomechanical exploration was made and a plantar support was produced to avoid the reappearance of the injury because of local hyperpressure.

Lymphoepithelioma-like gastric carcinoma presenting as giant ulcer of the lesser curvature. Case report

Lymphoepithelioma-like gastric carcinoma (LELGC) has special clinicopathologic features that differentiate it from the common gastric adenocarcinoma. LELGC is a rare neoplasm of the stomach with an incidence of 1-4% of all gastric cancers and is characterized by desmoplastic stroma uniformaly infiltrated by abundant lymphocytes and plasma cells. LELGC is closely associated with the Epstein-Barr virus (EBV), with 80-100% of LELGC being EBV-positive. LELGC has a male predominance, occurs in elderly people and is usually located in the upper and middle portion of the stomach. We report a rare case of lymphoepithelioma-like gastric carcinoma located in the lesser curvature at the border of the gastric body to the pyloric antrum.