Blockade of autocrine stimulation in simian sarcoma virus-transformed cells reverses down-regulation of platelet-derived growth factor receptors.

The viral (v)-sis oncogene encodes a protein (p28sis) that is structurally homologous to platelet-derived growth factor (PDGF). We have shown that simian sarcoma virus (SSV)-transformed cells containing the v-sis oncogene release a Mr 20,000 substance that is recognized by antisera to synthetic peptide sequences contained in p28sis. Medium conditioned by SSV-transformed cells competes with 125I-labeled PDGF for specific PDGF receptor sites, initiates DNA synthesis, and stimulates tyrosine phosphorylation of the PDGF receptor when added to normal cells. When normal cells are co-cultured with SSV-transformed cells, the PDGF receptors of the normal cells are down-regulated by factors released from the transformed cells. Thus, SSV-transformed cells release material that is functionally similar to PDGF. We have used anti-phosphotyrosine antibodies to purify PDGF receptors and to detect PDGF-stimulated receptors in normal cells. SSV-transformed cells have no PDGF receptors detectable by these antibodies or by 125I-labeled PDGF binding studies. However, when SSV-transformed cells are exposed to suramin, a compound that blocks binding of PDGF to its receptors, the receptors reappear on the cell surface and within 8 hr are present at the same levels as in control cells. These "new" receptor sites can be phosphorylated in response to PDGF. Thus, the absence of PDGF receptors in SSV-transformed cells is due to down-regulation of the receptors by an autocrine mechanism that can be blocked by suramin.     

Alterations in intervertebral disc composition,matrix homeostasis and biomechanical behavior in the UCD‐T2DM rat model of type 2 diabetes

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis, and biomechanical behavior. Coccygeal motion segments were harvested from 6‐month‐old lean Sprague‐Dawley rats, obese Sprague‐Dawley rats, and diabetic obese UCD‐T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end‐product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia‐inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress, and AGE/RAGE‐mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:738–746, 2015.     

Exotic and indigenous problem plants species used,by the Bapedi,to treat sexually transmitted infections in Limpopo Province,South Africa

Background

The ethnic usage of exotics and indigenous problem plants is a highly debated topic, as legislative requirements over-shadow their potential medicinal value, particularly to treat sexually transmitted infections (STIs). Limited information exists regarding their medicinal value among the Bapedi.

Objectives

To ascertain the importance of exotics and indigenous problem plants in the treatment of STIs, a major global primary health care challenge.

Methods

A field observation and semi-structured questionnaire focussing on species diversity, types of STIs treated and medicinal preparation as well as application was used to collect data from 34 traditional healers.

Results

Seven exotics and three indigenous problem species were identified. These species were used to treat four STIs; with Catharanthus roseus illustrating its dominance in the treatment of gonorrhoea. Some medicinal species used by Bapedi traditional healers have been validated through scientific research or through their extensive use by various cultures in South Africa and other parts of Africa. To the best of our knowledge Alternanthera pungens, Caesalpinia decapetala, Cinnamomum verum, and Citrullus lanatus are reported for the first time in the treatment of the investigated STIs.

Conclusions

Exotic and indigenous problem species constitute an important component of the STIs treatment protocol. Their utilization by Bapedi cautions against the narrow-minded approach of indiscriminate eradication, as these species can play a significant role in the primary health care needs of socio-economic vulnerable people.     

Apolipoprotein E s4 Allele and Outcomes of Traumatic Spinal Cord Injury

Abstract

Background/Objective: To test the hypothesis that apolipoprotein E (APOE) polymorphisms are associated with outcomes after spinal cord injury (SCI).

Methods: Retrospective cohort study, from rehabilitation admission to discharge.

Participants: Convenience sample of 89 persons with cervical SCI (C3-C8) treated from 1995 through 2003. Median age was 30 years (range 14-70); 67 were male (75%) and 83 were white (93%).

Main Outcome Measures: American Spinal Injury Association (ASIA) motor and sensory scores, ASIA Impairment Scale (AIS), time from injury to rehabilitation admission, and length of stay (LOS) in rehabilitation.

Results: Subjects with an APOE s4 allele (n = 15; 17%) had significantly less motor recovery during rehabilitation than did individuals without an s4 allele (median 3.0 vs 5.5; P < 0.05) and a longer rehabilitation LOS (median 106 vs 89 days; P = 0.04), but better sensory-pinprick recovery (median 5.0 vs 2.0; P = 0.03). There were no significant differences by APOE s4 allele status in sensory-light touch recovery, likelihood of improving AIS Grade, or time from injury to rehabilitation admission.

Conclusions: APOE ε4 allele was associated with differences in neurological recovery and longer rehabilitation LOS. Genetic factors may be among the determinants of outcome after SCI and warrant further study.     

Behavioral Mediators of Treatment Effects in the Weight Loss Maintenance Trial

Background

The Weight Loss Maintenance Trial tested strategies for maintenance of weight loss. Personal contact was superior to interactive technology and self-directed conditions.

Purpose

We aimed to identify behavioral mediators of the superior effect of personal contact vs. interactive technology and of personal contact vs. self-directed arms.

Methods

Overweight/obese adults at risk for cardiovascular disease (n?=?1,032) who lost at least 4 kg were randomized to personal contact, interactive technology, or self-directed. After 30 months, 880 participants had data on weight and behavioral strategies.

Results

Reported increase of intake of fruits and vegetables and physical activity and more frequent self-weighing met criteria as mediators of the better outcome of personal contact vs. interactive technology. Increased intake of fruits and vegetables, more frequent self-weighing, and decreased dessert consumption were mediators of the difference between personal contact vs. self-directed.

Conclusion

Inducing changes in the identified behaviors might yield better outcomes in future weight loss maintenance trials. (ClinicalTrials.gov number NCT00054925)     

An Observational Cohort Study of the Adoption of Elastic Stable Intramedullary Nailing for the Treatment of Pediatric Femur Fractures in Kumasi,Ghana

Background

In high- and middle-income countries, elastic stable intramedullary nailing (ESIN) is the commonest treatment of femur fractures in children 5–11 years of age. At Komfo Anokye Teaching hospital (KATH) in Kumasi, Ghana, prior to this study all pediatric femur fractures were treated with skin traction to union. This study was designed to report the early results and costs of the adoption of ESIN at KATH to provide data to other low- and middle-income sites considering adoption of this surgical technique.

Methods

An observational cohort study that included 84 pediatric patients ages 3–14 years presenting with closed femur fractures and treated with either skin traction or ESIN. Multivariate logistic regression was used to compare the rate of treatment success between treatment groups.

Results

Treatment success (coronal and sagittal angulation less than 10 ° and shortening less than 15 mm at osseous union) was achieved in 92 % of the ESIN group versus 67 % of the skin traction group (odds ratio for ESIN group 9.28 (1.6–54.7); p = 0.0138). Average length of stay was significantly lower in the ESIN group (p = 0.001), but charges to patients were higher in the ESIN group (p < 0.001) because of the high cost of implants.

Conclusions

The initial experience of operative treatment of femoral shaft fractures in children using ESIN was positive, with improved rates of treatment success and no surgical complications. Because of the high cost of implants, direct costs of treatment remained higher with ESIN despite reductions in length of hospital stay.