Urinary Hydroxyproline Research Articles

Toxic effect of sodium fluoride on hydroxyproline level and expression of collagen-1 gene in rat bone and its amelioration by Tamrindus indica L. fruit pulp extract.

Excessive fluoride intoxication plays an important role in the development of dental, skeletal and non-skeletal fluorosis. The aim of this study was to ascertain the toxic effect of excessive fluoride ingestion on the level of hydroxyproline and expression of type 1 collagen gene in rat bone and its amelioration by supplementation with Tamarindus indica fruit pulp extract. Forty albino rats were randomly assigned to four groups. The first group served as control and received only tap water. The second group received sodium fluoride (200 ppm) through drinking water. The third group received T. indica fruit pulp extract (200 mg/kg body weight) alone and the fourth group received the T. indica fruit pulp extract (200 mg/kg body weight) along with fluorinated drinking water (200 ppm) daily by gavage for a period of 90 days. The level of hydroxyproline and expression of type 1 collagen gene using quantitative real time PCR in the tibia bone decreased significantly with continuous exposure to sodium fluoride. Co-administration of T. indica fruit pulp extract during exposure to fluoride through drinking water restored the level of calcium, phosphorus and alkaline phosphatase in serum and the concentration of hydroxyproline in urine. It increased the level of hydroxyproline and expression of type 1 collagen gene in the tibia as compared to untreated fluoride-exposed rats. It is concluded that T. indica fruit pulp extract has an ameliorative potential to protect the bone from fluoride induced collagen damage.

Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats

Background: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor γ. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. Methods: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. Results: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARγ and adipocyte protein 2 were downregulated. Conclusion: Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.

Application of Glutamine-enriched nutrition therapy in childhood acute lymphoblastic leukemia.

BackgroundWe investigated the effects of glutamine (Gln)-enriched nutritional therapy during chemotherapy on the nutritional status and immune function of children with acute lymphoblastic leukemia (ALL).MethodsWe enrolled 48 children who were newly diagnosed with ALL in our department during the period of 2013.1-2014.12. The patients (follow random number table) were randomly divided into the control group (peptamen) and the treatment group (peptamen + glutamine), 24 cases in each group. The remission induction regimens were all based on VDLP (D) chemotherapy (VCR (Vincrisstine), DNR (Daunomycin), L-ASP (L-Asparagiase), Prednisolone and Dexamethasone). The treatment group received Gln-enriched nutritional therapy every day during the full course of chemotherapy,and the control group is as same as the treatment group except without glutamine. The indicators of general nutritional status, such as weight, height, and triceps skinfold thickness, and the indicators of biochemical tests, such as serum albumin, prealbumin, creatinine-height index, retinol binding protein, and urinary hydroxyproline index, were compared between the two groups at the end of the first, second, third and the fourth week when the chemotherapy was completed. And in the fourth week, flow cytometry was applied to detect the levels of T cell subsets and the activities of natural killer (NK) cells in peripheral blood of the two groups.Results1. after 4 weeks nutritional therapy, there is no significant difference (p > 0.05) between the two groups of children in weight, height and other indicators. 2. At the end of 2 weeks treatment, the level of prealbumin (PA) and retinol-binding protein (RBP) is higher in treatment group than that in the control group (P <0.05), at the end of 3 weeks treatment, the thickness of triceps skinfold is higher (P <0.05) than that in the control group; 3. At the end of 3 and 4 weeks, the concentrations serum ALB, PA, RBP and UHI were higher than in the control group (P <0.05); 4. There is statistically significant (p < 0.05) between the two groups in edema incidence; 5. At the end of treatment (4 weeks), the percentages of CD3 +, CD4 +, CD4 +/CD8 +, NK cell are significantly decreased in the two groups (P <0.05).ConclusionGln-enriched nutritional therapy can effectively improve the systemic nutritional status of children with leukemia, improve immune function.

URINARY HYDROXY-PROLINE ESTIMATION IS CHEAP BIOCHEMICAL MARKER OF BONE TURNOVER IN POST MENOPAUSAL WOMEN

Aim: To estimate urinary hydroxy- proline in pre and post menopausal Women as a marker of bone resorption. Materials and methods: This is a prospective, observational study of 25 healthy post menopausal women with 25 healthy premenopausal women as control conducted at Gandhi Hospital Secunderabad. The study period was between June 2008 to June 2010. 24 hours urinary Hydroxyproline was measured in both cases and controls. Results: The mean urinary Hydroxyproline in Post menopausal women was 31.64 with standard deviation of 3.37. The mean urinary Hydroxyproline in Pre menopausal women was 19.61 with standard deviation of 2.34. It has got the statistical significance with p value of <0.0001 Discussion: Fibrillar collagens are rich in the amino acid hydroxyproline, which is excreted in the urine after collagen degradation and are considered to be markers of bone resorption. The urinary excretion of hydroxy proline is increased in states of physiologically high turnover, such as somatic growth, during menopause and high turnover osteopathies.This increased excretion is due to increase in bone loss which was a characteristic feature of the postmenopausal period.Our results show that urinary hydroxy proline was increased in postmenopausal women compared to premenopausal controls and also urinary hydroxy proline levels were increased more in late postmenopausal women than in early postmenopausal women. Conclusion: In Postmenopausal women with osteoporosis biochemical markers of bone formation decrease and biochemical markers of bone resorption increases. This is because there is more osteoclastic activity.In our study in post-menopausal women urinary hydroxy proline level was found to be elevated when compared to pre-menopausal group. Key words : Post menopausal women, Pre menopausal women, Hydroxyproline, Osteoporosis.

The combined effect of laser and oral administration of Iranian propolis extract on skin wound healing in male rats

Background: To date, a lot of research has been carried out on the effect of medications and surgical methods on the treatment of wounds, but no ideal achievement has been obtained yet. This study was conducted to investigate the single and combined effect of laser and propolis on skin wound healing in male rats. Methods: 40 Wistar male rats (200-250 g) were divided into 4 groups (n= 10). All animals were anesthetized and sterile skin wound was created by surgical scissors. Control group had no treatment, the second group was treated with laser (10 mW), the third group was treated with oral propolis (100 mg /kg; 3 times /day) and the forth group was treated with both laser and propolis. The wound healing level was measured based on the wound area and urinary hydroxyproline content. Results: Urinary hydroxyproline content was increased in groups treated with laser, propolis and combined laser and propolis compared to the control group (P<0.01, 0.05 and 0.01, respectively). Also at the end of the treatment period, the wound extent was significantly lower in the laser, propolis, and combined laser and propolis groups than the control (P<0.05, 0.05 and 0.01, respectively). There was no significant difference between treatment groups. Conclusion: Our results showed that oral administration of propolis or low power laser radiation can increase the wound healing rate.

Combination of low dose major n3 PUFAs in fresh water mussel lipid is an alternative of EPA–DHA supplementation in inflammatory conditions of arthritis and LPS stimulated macrophages

This article deals with the nutritional aspect of fresh water mussel Lamellidens marginalis and its pharmacological potential in inflammatory disorders. Fresh water mussel extract shows anti-inflammatory activity after oral supplementation. Therefore, the present work was aimed to elucidate anti-inflammatory activity of Lamellidens lipid in in vivo adjuvant induced arthritis and in vitro LPS induced macrophage activation model, where its activity was compared with pharmaceutical grade EPA–DHA supplement. Parameters that showed better response to mussel lipid, than to EPA–DHA supplement, were paw and ankle diameters, paw weight, urinary hydroxyproline, glucosamine, serum phosphatases, macrophage lipid peroxidation level and pro-inflammatory interleukin level in adjuvant induced arthritis and TNFα, NO level, intracellular ROS generation as well as nuclear translocation of NFκB p65 in LPS activated in vitro primary macrophage culture. Fresh water mussel lipid was found to have lower n3:n6 ratio than that in marine species but contain all the major n3 fatty acids. This study, for the first time, showed anti-inflammatory potential of lipid from a fresh water species. It has also raised the possibility of the presence of balanced fatty acid combination in a dietary dose, rather than the established EPA–DHA supplement, to be more effective against inflammatory conditions of arthritis and LPS stimulated macrophages.

Evaluation of anti-inflammatory, anti-nociceptive, and anti-arthritic activities of Indian Apis dorsata bee venom in experimental animals: biochemical, histological, and radiological assessment

Traditionally venoms are used from thousands of years to treat pain, inflammation, and arthritis. In Ayurveda “Suchika Voron” and “Shodhona” were practiced against pain.In the present study, venom composition of the Indian honeybee Apis florea (AF), Apis dorsata (AD), and Apis cerana indica (AC) were analyzed using electrophoresis (SDS-PAGE). This venom analysis was used to shed light upon the correlation in structure and the venom composition among the three species in Indian fields.Among the three species, Indian Apis dorsata bee venom (ADBV) is evaluated for an anti-inflammatory, anti-nociceptive activity, and antiarthritic activity in different animal models. The effect of ADBV is revealed for its anti-arthritic activity in the FCA- and CIA-induced arthritis model in male Wistar rats. The immunosuppressant action of ADBV was studied by hemagglutination antibody titer. It has been found that ADBV possesses anti-inflammatory and antinociceptive activities. In FCA- and CIA-induced arthritis, ADBV able to decrease rheumatoid factor, pain perception parameters, C-reactive protein, erythrocytes sedimentation rate, urinary hydroxyproline, serum transaminase level, and serum nitric oxide level when compared with diseased control arthritic rats. IL-6, TNF-α level was found to be decrease by ADBV treatment in collagen induced arthritis model. Thus this study confirmed the scientific validation behind utilization of venom in Indian Apis dorsata bees in arthritis and inflammatory diseases which has been not reported till date.

24 Hours Urinary Hydroxyproline - A Noninvasive, Cost-Effective and Early Biochemical Marker Which May be Used to Screen the Osteoporotic Lesion in Postmenopausal Women

Introduction: Osteoporosis results due increased rate of bone turnover. It has multifactorial etiology and most common in women after menopause. Objective: The current study was aimed to assess the rate of bone turnover towards detection of osteoporotic changes by measuring 24 hours urinary hydroxyproline which is an early as well as non- invasive biochemical bone marker. Methods: Urinary hydroxyproline was measured in 40 postmenopausal women and compared with similar number of premenopausal women as controls. Results: 24 hours urinary hydroxyproline levels were significantly higher (p&lt;0.001) in postmenopausal women than premenopausal groups. This indicates a higher rate of bone turnover suggesting osteoporotic changes. 24 hour urinary hydroxyproline is also positively correlated (r= 0.934) with age. Conclusion: The present study suggests that measurement of 24 hours urinary hydroxyproline which is a cost-effective and non- invasive technique, may be used for screening and early detection of osteoporotic changes in women of postmenopausal age group.DOI: http://dx.doi.org/10.3126/ajms.v6i4.11853 Asian Journal of Medical Sciences Vol.6(4) 2015 21-24

Changes in biochemical markers in blood and urine in case of malunion and nonunion after fracture of long bones

Background: Biochemical markers provide a dynamic view of the remodeling process of bone. Aims: To monitor biochemical markers in long bone fractures as they reflect the actual status of fracture healing. Materials and Methods: The present study after taking Institutional ethical clearance and informed consent of the subjects. Patients with normal fracture union served as controls (50); Patients with impaired fracture union served as cases. They were further divided into two groups: Fracture nonunion (20) and fracture malunion (30). Serum calcium, serum alkaline phosphatase (ALP), urinary calcium to creatinine ratio, and urinary total and free hydroxyproline were measured. Results: Serum ALP, serum calcium, urinary total and free hydroxyproline, and urinary calcium to creatinine ratio were increased in all patients after fracture. Serum ALP, urinary total and free hydroxyproline decreased after treatment in nonunion patients. Serum ALP reached to lower level of reference interval in this group. But urinary total and free hydroxyproline decreased to less than normal level. Serum calcium increased up to 2 weeks following treatment and then reduced to normal level within 1-month in fracture normal union and malunion groups. Serum calcium reduced at a very slow rate after treatment in nonunion patients and remained within reference interval. Significant differences were found between normal union and nonunion groups in case of serum ALP, urinary total and free hydroxyproline levels after treatment. Significant differences were found between normal union and nonunion groups in serum calcium level after treatment on day 7 and 14. Conclusions: Serial monitoring of biochemical markers of bone turnover reflect the actual status of bone resorption and bone formation, respectively. Thus, they can be used as an adjunct to clinical and radiological evidence of fracture healing.

Correlation between Vitamin C Deficiency and Hydroxyproline Amino Acid in Young Children of Northern Part in Palestine

Vitamin C is a water soluble vitamin found in many natural sources, citric fruits, vegetables, particularly as antioxidants and as a factor to catabolism and metabolism. The aim of this article is to correlate the level of vitamin C and the hydroxyproline level in urine samples among young palestinian children from age 5 - 14 years. Materials and Methods: Urine samples of 34 individuals of both sexes, their ages ranged from 5 - 14 years were collected and analyzed for determination of Urinary Hydroxyproline by using Modified Neuman and Logan Method. The result of this study shows a significant correlation between Vitamin C and Hydroxyproline at level 0.01. The conclusion of this study was that low vitamin C intake was found among young palestinian children from age 5 - 14 years, Vitamin C should be supplemented in the drinks taken by young palestinian children from age 5 - 14 years as well as further research and investigation with large samples required to include all children from middle and southern Palestine.

SOURCE, CHEMISTRY, METABOLISM, PHYSIOLOGICAL FUNCTION: ASCORBIC ACID WITH HUMAN HEALTH

Ascorbic acid commonly known as Vitamin C and it is water soluble vitamin having Antioxidant characteristics, abound in nature and highly labile.it is very important Vitamin for biosynthesis of collagen, carnitine and neurotransmitters. Some plants and animals synthesised this Vitamin but human, apes and some other are not able to synthesis this Vitamin due to lack of Gulonolactone oxidase enzyme. So, this Vitamin is supplemented by outer source like fruit, vegetable and synthetic pharmaceutical products. The current US recommended dietary allowances (RDA) for Ascorbic acid is 100-120 mg/day. Ascorbic acid has many biochemical functions like Antioxidant, Anti-antherogenic, Anti-carcinogenic, immunodulator and its preventing cold. It’s also associated with reduction of incidence of cancer, immunity, blood pressure, drug metabolism and urinary hydroxyproline excretion, tissue regeneration. Mainly it shows effective result in gastric cancer. Ascorbic acid decreases the death risk. Now day, This Vitamin is used in nutraceutical in human biology and health. Keywords: Ascorbic acid, Gulonolactone oxidase, antiantherogenic.

Experimental study of the effect on bone metabolism and bone histomorphometry of osteoporosis rats with birdpecking and revolving moxibustion on twelve back-shu points.

The aim of the study was to explore the effect of birdpecking and revolving moxibustion on twelve back shenshu points on the bone metabolism and bone histomorphometry of osteoporosis rats. The 50 female rats of 8 months old that did not pregnant were collected and randomly divided into sham-operation group, model group, moxibustion group, moxibustion and estrogen group, and estrogen group. All the rats, except for the rats in the sham-operation group, received ovarian surgery to establish the models. After 10 days postoperatively (healing), the rats received moxibustion and estrogen therapy. According to the different groups, the rats received rat femur in vivo bone mineral density assessment at 90 days after surgery. After that, the rats were sacrificed, and then the left femoral bones were collected for bone histomorphometry test; blood was taken for bone alkaline phosphatase (BALP) testing, and urine was collected for hydroxyproline testing. The urine hydroxyproline was tested once at 24 h after ovarian surgery. At 24 h after ovarian surgery, the urine hydroxyproline in the ovariectomy group was significantly higher than that in the sham-operation group (P < 0.05), indicating that after ovarian surgery, the collagen broke down which accelerated the process of osteoporosis. After the intervention therapy with moxibustion and estrogen, the BALP, urinary hydroxyproline and femoral bone histomorphometry were comparatively analyzed, and the results showed that the intervention groups were higher than the model group (P < 0.05). But when compared with the sham-operation group, the indexes in the intervention groups were decreased, and the differences were significant (P < 0.05), indicating that intervention could only delay the incidence of osteoporosis. The Chinese traditional measure of "birdpecking and revolving moxibustion on twelve back-shu points" can effectively prevent the recession of bone metabolism of osteoporosis rats, and slow down the degeneration of bone morphology, which can be used to delay the incidence of osteoporosis.

Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus.

Sclerostin is an osteocyte-derived inhibitor of the Wnt/β-catenin signaling pathway, which acts as a negative regulator of bone formation. Published data on sclerostin levels in type 1 diabetes mellitus (T1DM) are few. To evaluate gender differences in sclerostin serum levels and the association among sclerostin, bone mass, bone metabolism, and the main clinical characteristics of subjects with T1DM. A total of 69 patients with T1DM (mean age, 33.7±8.1; 49% males) were enrolled in this cross-sectional study in a clinical research center. Bone mineral density was measured by phalangeal quantitative ultrasound (QUS); bone turnover markers (urinary pyridinoline, deoxypyridinoline (D-PYR), and urine hydroxyproline (OH-PRO) to evaluate bone resorption; serum bone alkaline phosphatase and BGP to evaluate bone formation) and sclerostin were assessed. D-PYR and sclerostin were significantly higher in women when compared with men (P=0.04). A disease duration >15 years was associated with higher sclerostin levels (P=0.03). Bone turnover markers and QUS parameters were not correlated with sclerostin. A significant negative correlation was observed among QUS parameters, BMI, and OH-PRO. Sclerostin serum levels were correlated with homocysteine (r=-0.34, P=0.005) and vitamin B12 (r=-0.31, P=0.02). Generalized linear model showed that macroangiopathy was the only predictor of sclerostin serum levels (β=-11.8, 95% CI from -21.9 to -1.7; P=0.02). Our data demonstrate that women with T1DM exhibit higher sclerostin levels than men and that circulating sclerostin is not associated with bone turnover markers and phalangeal QUS measurements. Macroangiopathy was associated with sclerostin levels.

A comparative study between the effect of 17-β estradiol and antioxidants combination on some menopausal changes in oophorectomised rats

As oxidative stress is proposed to be responsible for many of the menopause associated disorders, antioxidants may play an important role in this situation. The aim of this work was to compare between the effects of oestrogen replacement therapy and antioxidant supplements of vitamin C and low dose of vitamin A on some menopause associated changes in oophorectomised rats. Forty albino female rats were divided into 4 groups: normal control group, oophorectomised group, oophorectomised group treated with 17-β estradiol (oophorectomised + E 2 ) and oophorectomised group treated with vitamins (oophorectomised + vit).The following were measured: total antioxidant (TAO) and malondialdehyde (MDA), lipid profile, serum insulin, glucose and homeostasis model assessment-insulin resistance (HOMA-IR), bone specific alkaline phosphatase (BALP), urinary hydroxyproline, weight gain and visceral fat. A positive correlation was found between MDA and low density lipoprotein-cholesterol (LDL) ( r = 0.694 and P = 0.000), HOMA-IR ( r = 0.691 and P = 0.000.) and BALP ( r = 0.563 and P = 0.000) and urinary hydroxyproline level ( r = 0.761 and P = 0.000). Those results denoted that OS might be a cause of dyslipidemia, insulin resistance and osteoporosis associated with menopause. Both E 2 and vitamins in oophorectomised rats led to a significant decrease in MDA ( F = 33.402, P = 0.000), weight gain, visceral fat ( F = 7.589, p = 0.000 and F = 3.748, P = .019, respectively), cholesterol ( F = 40.748, P = 0.0001), LDL cholesterol ( F = 55.168, P = 0.0001), and significant increase in HDL ( F = 18.393, P = 0.0001) and TAO levels ( F = 14.781, P = 0.000) compared to oophorectomised rats. Also, both treatments led to a significant decrease of HOMA-IR ( F = 18.933, P = 0.000, respectively), BALP ( F = 13.202, P = 0.000) and urinary hydroxylproline ( F = 220.012, P = 0.000). An interesting finding was detected where oophorectomised rats showed a decrease in triglyceride level which was significantly increased by E 2 administration whereas antioxidant administration produced no change ( F = 34.267, P = 0.0001). Our results denote similar effects of both E 2 and antioxidant’ supplements (vitamin C and low dose vitamin A) administration in surgically induced menopause in rats regarding oxidative stress, weight gain, atherogenic lipid profile changes, insulin sensitivity and bone turnover. However differences between preclinical and clinical studies must be taken into consideration especially when moving from animal studies to clinical trials.

DETERMINATION OF PROLINE, HYDROXYPROLINE, AND N–ETHYLGLYCINE IN URINE BY USING A NEW HPLC LABELING REAGENT, AND ITS APPLICATION IN DETECTION OF TUMOR MARKERS

According to previous reports, the concentration of urinary proline (Pro), hydroxyproline (Hyp), and N-ethylglycine (Neg) varies in association with various diseases, especially, Neg as a tumor marker was recently found in association with bone metastasis cancers. We developed a low-cost, highly sensitive precolumn high–performance liquid chromatography (HPLC) method for simultaneous determination of Pro, Hyp, and Neg in urine of patients with cancers, bone metastasis cancers, and bone metastasis cancers that have appeared after radiotherapy and chemotherapy treatment. The analytes in the urine were labeled with 4–methoxybenzenesulfonyl fluoride (MOBS–F) at 40°C. The derivatives were separated on a reversed-phase column by gradient elution and monitored with ultraviolet (UV) detection at 232 nm. The detection limits for Pro, Hyp, and Neg were 6.0 pmol/injection, 4.0 pmol/injection, and 50 pmol/injection (S/N = 3), respectively. To some extent, Neg levels in their urine show there were relevance to their health conditions or therapy progress. We believe that the developed method may be a promising measure for providing a useful reference to diagnose the illness and monitor the results for bone metastasis cancers after radiotherapy and chemotherapy treatment.

Therapeutic Effects of Acetone Extract of Saraca asoca Seeds on Rats with Adjuvant-Induced Arthritis via Attenuating Inflammatory Responses.

Saraca asoca has been traditionally used in Indian system for treatment of uterine, genital, and other reproductive disorders in women, fever, pain, and inflammation. The hypothesis of this study is that acetone extract of Saraca asoca seeds is an effective anti-inflammatory treatment for arthritis in animal experiments. The antiarthritic effect of its oral administration on Freund's adjuvant-induced arthritis has been studied in Wistar albino rats after acute and subacute toxicities. Phytochemical analysis revealed presence of high concentrations of phenolic compounds such as flavonoids and tannins, while no mortality or morbidity was observed up to 1000 mg/kg dose during acute and subacute toxicity assessments. Regular treatment up to 21 days of adjuvant-induced arthritic rats with Saraca asoca acetone extract (at 300 and 500 mg/kg doses) increases RBC and Hb, decreases WBC, ESR, and prostaglandin levels in blood, and restores body weight when compared with control (normal saline) and standard (Indomethacin) groups. Significant (P < 0.05) inhibitory effect was observed especially at higher dose on paw edema, ankle joint inflammation, and hydroxyproline and glucosamine concentrations in urine. Normal radiological images of joint and histopathological analysis of joint, liver, stomach, and kidney also confirmed its significant nontoxic, antiarthritic, and anti-inflammatory effect.

Prevention of Arthritis Markers in Experimental Animal and Inflammation Signalling in Macrophage by Karanjin Isolated fromPongamia pinnataSeed Extract

Karanjin, the furanoflavonoid reported to possess gastroprotective and anti-diabetic properties, was investigated against experimental arthritis and its molecular signalling in inflammation was explored in macrophages. Karanjin was isolated from hexane extract of Pongamia pinnata seeds and was evaluated on arthritis markers in adjuvant induced arthritis model (AIA) in two doses (per oral; 10 mg/kg/day and 20 mg/kg/day). Karanjin dose dependently reduced collagen and cartilage breakdown markers viz. urinary hydroxyproline and glucosamine, respectively, serum lysosomal enzymes responsible for articular cartilage damage, and major proinflammatory cytokine TNFα, secreted by macrophages involved in articular inflammation and destruction. Karanjin also prevented joint damage as evidenced from arthritis score, radiographic and histopathological analysis. To delineate the molecular target of Karanjin, in vitro study on LPS induced macrophages were performed at calibrated non toxic doses (4 µg/mL and 6 µg/mL). Karanjin reduced TNFα production and also showed potent inhibitory effect on nitric oxide and reactive oxygen species production which is generally induced by TNFα from activated macrophages. NF-κB, the key regulator of TNFα signalling during inflammation was significantly suppressed by Karanjin. Our study for the first time highlights the anti-inflammatory role of Karanjin in experimental arthritis model as well as on macrophage signalling, thereby depicting its probable mechanism of action.

Lead exposure is a risk for worsening bone mineral density in middle-aged male workers

Objective: Lead exposure linked to osteoporosis in women. However, there is no direct evidence whether lead exposure has effects on bone metabolism in middle-aged male subjects. Therefore, the present study investigated the relationship between bone mineral densitometry measurements, bone markers, endocrine hormones and blood lead levels.Material and methods: The present study included lead exposure patients (n: 30) and control subjects (n: 32). We recorded information on patient demographics and risk factors of osteoporosis. Blood lead levels were evaluated using Varian AA 240Z atomic absorption spectrophotometry. Bone mineral density measurements were measured using dual-energy X-ray absorptiometry.Results: Each lumbar T and Z scores in the lead exposure group were lower than the control group. There were no significant differences in femur neck and femur total T and Z scores between two groups. Blood lead levels were also negatively correlated with lumbar 2-4 T score, total lumbar T score, lumbar 2-4 Z score and total lumbar Z score. Urinary hydroxyproline and urinary deoxypyridinoline levels in the lead exposure group were significantly higher compared to controls. Blood lead levels were strong, positively correlated with urinary deoxypyridinoline. Endocrine hormone levels and 1,25-dihydroxy-vitamin D3 levels were comparable between lead exposure and control group.Conclusion: Lead exposure in male workers is an important factor for deterioration in bone mineral density. We should be screening blood lead levels and history of lead exposure in male osteoporosis.

Suppression of NF-κB p65 nuclear translocation and tumor necrosis factor-α by Pongamia pinnata seed extract in adjuvant-induced arthritis

Pongamia pinnata is a plant known for its therapeutic usage in Indian traditional medicine. Despite the controversy regarding toxic flavonoid and erucic acid content, the seed of this plant is consumed in tribal medicine and its oil is used in Ayurveda to treat psoriasis and arthritis. This study explored the potential anti-arthritic effects of a P. pinnata seed (hexane) extract (PSE) at non-lethal doses in an adjuvant-induced arthritic rat model; possible mechanisms of any observed effects were also explored. After establishing the lethal doses arising from oral exposure to the extract, the material was administered per os daily at two doses (0.3 g/kg/day; 0.5 g/kg/day) to arthritic rats. Other rats received indomethacin or vehicle (control). Treatments were performed for a total of 14 days. One day after the final exposure, the rats were euthanized to permit harvest of various cells, blood, and tissues for analyses. Paw diameter and tissue myeloperoxidase activity in the paws were evaluated as indices for edema and neutrophil infiltration into the tissue. The severity of arthritis in the experimental rats was assessed via measures of urinary hydroxyproline (HP) and glucosamine, and of serum pro-inflammatory TNFα and anti-inflammatory IL-10. The extent of NF-κB p65 nuclear translocation in peritoneal macrophages harvested from naïve rats and then treated in vitro was also assessed. The results indicated that exposure to PSE significantly decreased paw diameter, tissue myeloperoxidase level, and levels of urinary HP and glucosamine, as well as of serum TNFα and IL-10 in adjuvant-injected (arthritic) rats. In vitro PSE treatment also resulted in a marked inhibition of NF-κB p65 nuclear translocation in primary cultures of peritoneal macrophages. Thus, PSE appears to be able to prevent experimental arthritis, in part, by helping to maintain the balance between pro- and anti-inflammatory cytokines and by inhibiting NF-κB activation.

English

BACKGROUND: Disease of the bone, particularly osteoporosis, represents a major health care problem predominantly affecting women. There are various markers of bone turnover including markers for bone formation and bone resorption. Osteocalcin is a bone Gla protein synthesized by osteoblasts is found to increase in osteoporosis. In our study serum osteocalcin level was measured in pre and post menopausal women and also in osteoporotic women. MATERIALS & METHODS: Ninety individuals were included in this study and classified as three groups. Group A - 30 Pre menopausal women, Group B - 30 Post menopausal women and Group C - 30- Osteoporosis women. The above subjects were confirmed by Dexa Scan for osteoporosis. Serum sample was collected and osteocalcin were measured in all women by ELISA method. RESULTS: The serum Osteocalcin level was found to be increased in post menopausal and Osteoporotic individuals when compared to the pre menopausal women. CONCLUSION: The increased level of serum osteocalcin in post menopausal women may be a predictor for future risk for osteoporosis. To support this view, an extended study is absolutely essential. INTRODUCTION: The ultimate challenge facing health care providers is the quest for comprehensive treatments for chronic diseases within a framework of reduced patient access and limited financial resources. Osteoporosis is one of those diseases. Osteoporosis is a disease characterized by low bone mass and by architectural deterioration of bone tissue, the two factors related to abnormalities of bone turnover1. It is easy to diagnose osteoporosis in a patient with fracture. A more difficult but potentially more important approach is to diagnose osteoporosis before the occurrence of fracture. Basic and molecular studies of skeletal remodeling system have produced a wealth of new information about the osteoporotic process. Clinical studies employing new bone specific agents have generated tremendous enthusiasm for newer therapeutic options as well as providing a greater understanding of the spectrum of metabolic bone diseases. This expanded knowledge base has set the stage for even greater technological thrusts aimed at earlier diagnosis and cost effective treatment2. Bone formation and bone resorption are altered in most metabolic diseases like osteoporosis. The abnormalities have been characterized by bone histo-morphometry on iliac crest biopsy which allows both quantitative assessment of bone turnover at the cell and tissue level. Until recently the only available markers were total serum alkaline phosphatase for monitoring bone formation and urinary hydroxyproline for monitoring bone resorption. Both of them are not specific for bone tissue, as they are unable to detect the small increase in bone turnover. To overcome these problems, efforts were made in recent years to develop new and more specific markers of bone turnover. The rate of bone formation or degradation can be assessed by measuring the enzyme activity of osteoblastic or osteoclastic cells or by measuring components of the bone matrix released