New developments in animal models of Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by deterioration in mental function leading to dementia, deposition of amyloid plaques and neurofibrillary tangles (NFTs), and neuronal loss. The major component of plaques is the amyloid-b peptide (Ab), whereas NFTs are assemblies of hyperphosphorylated forms of the microtubule-associated protein tau. Electron microscopy of NFTs reveals structures known as paired helical filaments (PHFs). In familial AD (FAD), mutations in three distinct genes drive Aβ synthesis by favoring endoproteolytic secretase cleavages that liberate Aβ from the Alzheimer b-amyloid precursor protein (APP). This suggests that excess Ab initiates a pathogenic cascade in humans that culminates in all the pathologic and cellular hallmarks of AD. Building upon the knowledge of FAD mutations, incremental technical advances have now allowed reproduceable creation of APP transgenic mice that exhibit AD-like amyloid pathology and Aβ burdens. These transgenic mouse lines also exhibit deficits in spatial reference and working memory, with immunization against Aβ abrogating both AD-associated phenotypes. Besides establishing a proof of principle for Ab-directed therapies, these findings suggest a potential to identify individual elements in the pathogenic pathway that lead to cognitive dysfunction. Furthermore, transgenic APP mice with potent amyloid deposition will likely form a beachhead to capture the final elements of AD neuropathology—cell loss and NFTs composed of PHFs—that are missing from current transgenic models.     

Psychometric Properties of Osteoporosis Knowledge Tool and Self-Management Behaviours Among Malaysian Type 2 Diabetic Patients

Osteoporosis is a major growing public health problem and it is clear that much needs to be done to bridge the gap between patients and practitioners. However, the educator must have a valid and reliable tool to evaluate the effectiveness of the teaching and learning that are done. Osteoporosis Knowledge Tool (OKT) provides an important strategy for healthcare professionals to start early intervention for patients who are at risk of osteoporosis. The aims of this study were to translate and examine the psychometric properties of the Malaysian version of the Osteoporosis Knowledge Tool (OKT-M) among 250 type 2 diabetes patients and to assess factors that affect diabetic patients’ osteoporosis knowledge. The OKT English version was translated and validated using the internationally accepted and recommended methodology. The sensitivity and specificity of OKT-M was calculated using receiver operating characteristic curve analysis. The face and content validity showed acceptable results. Internal consistency, test–retest reliability, mean difficulty factor and discriminatory power values were 0.72, 0.83, 0.47 ± 0.16 and 0.96, respectively. The cut-off point of the OKT-M to predict osteoporosis/osteopenia was 14 with optimal sensitivity (84.1 %) and specificity (85.5 %). Regression analysis revealed that health belief, self-efficacy and some demographic data had an impact on the OKT-M. The findings of this validation study indicate that the OKT-M is a reliable and valid tool with good psychometric properties in the Malaysian setting. The OKT-M is an appropriate tool for application in clinical setting to identify patients need for a bone health-promoting intervention regarding lifestyle behaviour changes.     

Opposite effect of human chorionic gonadotropin on placental and ovarian synthesis of androstenedione

In the present studies, we have investigated the role of human chorionic gonadotropin on the biosynthesis of androgens by placentas and corpora lutea of the pregnant rat. We first sought to compare the effect of hCG on placental and ovarian secretion of androstenedione in vivo. For this purpose either 1.5 IU hCG or vehicle was administered to pregnant rats twice on days 12 and 13 and once on the morning of day 14. Blood was obtained from either the ovarian or the uterine vein. After hCG administration, levels of androstenedione secreted in the ovarian vein increased dramatically, whereas those in the uterine vein declined significantly. To establish that changes in androgen levels in the uterine and ovarian veins are due to changes in biosynthetic activity and also to compare the action of hCG on placentas and corpora lutea, tissues were dissected out from rats treated with 0, 1.5, or 9 IU hCG twice daily and incubated in vitro. hCG administration increased the capacity of luteal cells to synthesize androstenedione de novo by approximately 100% and concomitantly decreased placental secretion of androstenedione by approximately 75%. Addition of high density lipoprotein to the medium enhanced both basal and hCG-stimulated androstenedione production by luteal tissues but had no effect on either basal or hCG-inhibited androstenedione biosynthesis by the placenta. To determine which step in the placental biosynthesis of androstenedione is inhibited by increased levels of LH, we determined the effect of hCG administration, on cholesterol biosynthesis and storage, synthesis of progesterone substrate, and the activities of 17 alpha-hydroxylase/17,20-lyase. hCG did not affect the activities of the rate limiting cholesterogenic enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, placental content of cholesterol and cholesteryl ester, or the placental production of progesterone. However, hCG did cause a substantial decrease in the activity of 17 alpha-hydroxylase/17,20-lyase enzyme(s); responsible for the conversion of progesterone to androgen. In summary, results of the present investigation demonstrate that increases in LH activity in the circulation act on two different steroidogenic glands to either enhance or reduce androgen biosynthesis. hCG stimulates luteal secretion of androstenedione and simultaneously inhibits placental production of this steroid.(ABSTRACT TRUNCATED AT 400 WORDS)     

Radiographic features predictive of patellar maltracking during total knee arthroplasty

Despite improvements in component design and surgical technique, some patients still require lateral retinacular release during TKA to improve patella tracking. We studied 148 fixed-bearing TKAs to identify parameters in pre-operative knee radiographs that would predict intraoperative patellar maltracking. Digital radiographs and software were used to measure coronal alignment, distal femoral valgus angle, proximal tibia varus angle, patellar tilt, patellar shift, Insall–Salvati ratio, and patellar component placement and alignment. Patellar tracking was assessed after all components had been cemented, using both no-touch and modified “towel clip” techniques. The only radiographic parameter independently associated with maltracking was patellar shift. The median pre-operative patellar lateral shift in patients who had maltracking was 4.1 mm compared to 0.0 mm in those who did not. Patients who had a patellar shift of more than 3.0 mm had a high likelihood of maltracking, with estimated positive and negative predictive values of 78 and 95%, respectively. Pre-operative patellar shift may thus be clinically relevant for identifying osteoarthritic patients who have a higher likelihood for patellar maltracking during TKA. Variations in the intrinsic risk for maltracking within patient study populations may account for the widely differing reported rates of patellar maltracking, and our data suggest that information on pre-operative patellar shift may be helpful in stratifying these sample populations.     

Pretreatment with β‐adrenergic receptor agonists facilitates induction of LTP and sharp wave ripple complexes in rodent hippocampus

Norepinephrine, is involved in the enhancement of learning and memory formation by regulating synaptic mechanisms through its ability to activate pre‐ and post‐synaptic adrenergic receptors. Here we show that β‐agonists of norepinephrine facilitate the induction of both associational LTP and sharp wave ripples (SPW‐Rs) in acute slices of rat hippocampus in area CA3. Surprisingly, this facilitating effect persists when slices are only pretreated with β‐receptor agonists followed by wash out and application of the unspecific β‐adrenoreceptor (βAR) antagonist propranolol. During application of βAR agonists repeated stimulation resulted in facilitated induction of SPW‐Rs. Since SPW‐Rs are thought to be involved in memory replay we studied the effects of βAR‐agonists on spontaneous SPW‐Rs in murine hippocampus and found that amplitude and incidence of SPW‐Rs increased. These effects involve cyclic‐AMP and the activation of protein kinase A and suggest a supportive role in memory consolidation. © 2016 Wiley Periodicals, Inc.     

Effect of socio-demographic factors on endogenous biomarkers (cystatin C and creatinine) among elderly chronic kidney disease patients: a cross-sectional study

Purpose

Creatinine is normally used to evaluate kidney function among elderly patients in clinical practice, which has been reported to be affected by socio-demographic factors like BMI and age. Cystatin C a newly introduced biomarker may be more efficient in identifying kidney function in obese and aged CKD patients. The aim of the current study was to assess the effect of BMI on endogenous biomarkers (cystatin C and creatinine) among elderly CKD patients in Malaysia, a first such study in the country.

Methods

The current study was conducted at the Hospital University Sains Malaysia, Kelantan. A total of 300 elderly Malay participants ≥?65 years, with CKD, were taken in study. Demographic data, blood pressure, weight, and height were documented. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe Method), while serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader.

Results

The study participants were divided into three groups on the basis of age. There was a statistically significant difference at the p value?<?0.05 in serum creatinine level for the three age groups [F (2, 297)?=?1.98, p value 0.045]. Patients were divided into four groups on the basis of BMI. The results of one-way ANOVA revealed a statistically significant difference at the p value?<?0.05 in the mean serum creatinine level for the four groups [F (3, 396)?=?2.99, p value 0.032]. However, no statistically significant differences between mean serum cystatin C levels were observed on the basis of patient’s age and BMI.

Conclusion

Cystatin C is not related to BMI and age among elderly chronic kidney disease patients. The study clearly evaluates the role of serum cystatin C as a good competitor of creatinine among the elderly CKD patients.