Characterization of the interleukin 3 receptor

A variety of homobifunctional crosslinking agents have been used to gain insight into the nature of the murine interleukin 3 (mIL-3) receptor. When [125I]mIL-3 was cross-linked to receptor sites on the surfaces of intact B6SUtA1 cells with disuccinimidyl suberate (DSS), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed the existence of two radiolabeled species with molecular weights of 140 (p140) and 70 (p70) kd (after subtraction of [125I]mIL-3). The relative intensities of the two bands did not change when the [125I]mIL-3 concentration was varied, confirming Scatchard results which suggested only one affinity class. However, when [125I]mIL-3 was crosslinked to intact cells and then incubated at 37 degrees C, the intensity of p140 decreased relative to p70, suggesting a conversion of p140 to p70. This conversion could be inhibited by sodium azide, methylamine, and bacitracin and could also be prevented by first boiling for 1 min in 2% SDS and 5% 2-mercaptoethanol. The putative protease that carried out this apparent conversion appeared to be associated both with plasma membranes prepared from these cells and also with solubilized receptors. Moreover, when p140, crosslinked with both dithiobis succinimidylpropionate and glutaraldehyde, was purified and reelectrophoresed under reducing conditions, p70 could be generated. N-glycanase digestion of p140 and p70 revealed a similar level of N-linked carbohydrate, which upon closer study appeared to consist of two chains, a 3-kd and an 8-kd moiety. Consistent with this data, we propose that the receptor is a 140-kd glycoprotein that is cleaved to a 70-kd surface protein upon mIL-3 binding and chemical crosslinking.     

Proportion and Factors Associated with Depressive Symptoms among Elderly in an Urban Slum in Bangalore

Depression among elderly is emerging as an important public health issue in developing countries like India. Published evidence regarding the magnitude and determinants of depression among elderly hailing from urban slum is currently limited. Hence, the current study was conducted to assess magnitude of the problem and identify factors associated with depression among the elderly in an urban slum. A cross-sectional study was done to cover total of473 elderly persons from an urban slum in Bangalore, India. They were assessed for depression using Center for Epidemiologic Studies Depression scale. The overall prevalence of depression was found to be 37.8 (95 % CI = 33.43–42.16). Multivariate analysis revealed that unemployment (self or children) (odds ratio (OR) 2.6; 95 % confidence interval (CI) 1.41–4.72), illness of self (OR 2.2; 95 % CI 1.45–3.21), female gender (OR 1.9; 95 % CI 1.19–2.89), conflicts in family (OR 1.6; 95 % CI 1.03–2.43), and marriage of children or grandchildren (OR 1.6; 95 % CI 1.02–2.68) as independent risk factors. Depression among elderly is an important health issue of this area. Psychological intervention need to be provided for all elderly persons especially at the time of being diagnosed with any kind of illness. Strategies should be targeted to the females. The stressful life events need to be identified and remedial actions taken. This facility should be made available to them at the primary level of health care. There is a need to include screening of depression in our national health programs.     

Screening for coronary heart disease and diabetes risk in a dental setting

Objectives

Diabetes mellitus (DM) and heart disease, among the most prevalent chronic conditions worldwide, are increasing among younger adults who are unaware of their risk status. Previous studies in the United States have shown the efficacy of screening for risk of heart disease and diabetes in a dental setting. A screening strategy was applied to facilitate early identification of individuals at increased disease risk in a single Indian dental institute.

Methods

158 patients >30 years old, with no reported heart disease or diabetes, and unaware of any increased disease risk were enrolled. Blood pressure, total cholesterol, high-density lipoprotein levels and body mass index were collected. The Framingham Risk Score (FRS) was calculated as an indication of global risk of developing a coronary heart disease (CHD) event within 10 years; hemoglobin A1c level was used to determine DM risk.

Results

Eleven percent had increased risk of heart disease (FRS >10 %) and 32 % had abnormal A1c levels (>5.7 %). At least one risk factor was present in 61 and 39 % presented with two or more risk factors. Hypertension and obesity were the most common risk factors.

Conclusions

The use of a dental setting in a developing country could serve as a resource for early identification of patients at increased risk of developing CHD and DM, yet unaware of their increased risk. The dental setting can also serve as an entry point into the medical care system by identifying asymptomatic patients at increased risk of disease and referring these individuals to a primary care provider.     

Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca²⁺ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.     

Consultations with complementary and alternative medicine practitioners amongst wider care options for back pain: a study of a nationally representative sample of 1,310 Australian women aged 60–65 years

Back pain is a significant health service issue in Australia and internationally. Back pain sufferers can draw upon a range of health care providers including complementary and alternative medicine (CAM) practitioners. Women are higher users of health services than men and tend to use CAM frequently for musculoskeletal conditions. However, there remain important gaps in our understanding of women’s consultation patterns with CAM practitioners for back pain. The objective of this study is to examine the prevalence of use and characteristics of women who use CAM practitioners for back pain. The method used was a survey of a nationally representative sample of women aged 60–65 years from the Australian Longitudinal Study on Women’s Health. Women consulted a massage therapist (44.1 %, n?=?578) and a chiropractor (37.3 %, n?=?488) more than other CAM practitioners for their back pain. Consultations with a chiropractor for back pain were lower for women who consulted a General Practitioner (GP) (OR, 0.56; 95 % CI 0.41, 0.76) or a physiotherapist (OR, 0.53; 95 % CI 0.39, 0.72) than for those who did not consult a GP or a physiotherapist. CAM practitioner consultations for back pain were greater for women who visited a pharmacist (OR, 1.99; 95 % CI 1.23, 3.32) than for women who did not visit a pharmacist. There is substantial use of CAM practitioners alongside conventional practitioners amongst women for back pain, and there is a need to provide detailed examination of the communication between patients and their providers as well as across the diverse range of health professionals involved in back pain care.     

Preclinical Studies on Neurobehavioral and Neuromuscular Effects of Cocaine Hydrolase Gene Therapy in Mice

Cocaine hydrolase gene transfer of mutated human butyrylcholinesterase (BChE) is evolving as a promising therapy for cocaine addiction. BChE levels after gene transfer can be 1,500-fold above those in untreated mice, making this enzyme the second most abundant plasma protein. Because mutated BChE is approximately 70 % as efficient in hydrolyzing acetylcholine as wild-type enzyme, it is important to examine the impact on cholinergic function. Here, we focused on memory and cognition (Stone T-maze), basic neuromuscular function (treadmill endurance and grip strength), and coordination (Rotarod). BALB/c mice were given adeno-associated virus vector or helper-dependent adenoviral vector encoding mouse or human BChE optimized for cocaine. Age-matched controls received saline or luciferase vector. Despite high doses (up to 10¹³ particles per mouse) and high transgene expression (1,000-fold above baseline), no deleterious effects of vector treatment were seen in neurobehavioral functions. The vector-treated mice performed as saline-treated and luciferase controls in maze studies and strength tests, and their Rotarod and treadmill performance decreased less with age. Thus, neither the viral vectors nor the large excess of BChE caused observable toxic effects on the motor and cognitive systems investigated. This outcome justifies further steps toward an eventual clinical trial of vector-based gene transfer for cocaine abuse.     

[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.