Co-Adjuvancy of Solasodine & CoQ10 Against High Fat Diet-Induced Insulin Resistance Rats Via Modulating IRS-I and PPAR-γ Proteins Expression.

Insulin resistance (IR) is a condition in which target cells become insensitive to normal insulin concentrations in order to deliver glucose. The goal of this study was to see if solasodine combined with coenzyme Q10 could help rats with insulin resistance caused by a high-fat diet (HFD) by regulating the expression of IRS-I and PPAR-γ proteins.One of the six groups (n=6) got a conventional diet for 16 weeks as a control (normal), the HFD was given to the other five groups for 16 weeks, which further classified as-one group as HFD control while others treated with pioglitazone (10 mg/kg), coenzyme Q10 (50 mg/kg), solasodine (50 mg/kg) and combination of solasodine and coenzyme Q10i.e. SDQ10 (total 50 mg/kg) for the last 4 weeks orally once daily. Blood and tissue samples were collected by the end of study period for the biochemical and histological studies. As a result, HFD fed rats exhibited a significant increase in food and energy intake, body mass index, kidney and pancreas weight, fasting glucose, glycosylated haemoglobin, insulin level, liver enzyme ALT and AST and decrease antioxidant activity of superoxide dismutase and catalase. HFD received animals also produced a lower level of p-IRS1 and PPAR-y protein expression in western blot analysis. SDQ10 in combination successfully restored the above-mentioned complexity of insulin resistance caused by aHFD. Besides, increasesthe antioxidant activity of superoxide dismutase and catalase and normalized the architecture of kidney, pancreas and adipose tissue as well astreatment with SDQ10 raised the level of p-IRS1 and PPAR-y protein in liver tissue. As a result, supplementing with solasodine and coenzyme Q10 reversed the effect of the HFD on p-IRS1 and PPAR-y protein in liver tissue while also alleviating insulin resistance symptoms.

GWAS and ExWAS of blood mitochondrial DNA copy number identifies 71 loci and highlights a potential causal role in dementia.

Background: Mitochondrial DNA copy number (mtDNA-CN) is an accessible blood-based measurement believed to capture underlying mitochondrial (MT) function. The specific biological processes underpinning its regulation, and whether those processes are causative for disease, is an area of active investigation. Methods: We developed a novel method for array-based mtDNA-CN estimation suitable for biobank-scale studies, called 'automatic mitochondrial copy (AutoMitoC).' We applied AutoMitoC to 395,781 UKBiobank study participants and performed genome- and exome-wide association studies, identifying novel common and rare genetic determinants. Finally, we performed two-sample Mendelian randomization to assess whether genetically low mtDNA-CN influenced select MT phenotypes. Results: Overall, genetic analyses identified 71 loci for mtDNA-CN, which implicated several genes involved in rare mtDNA depletion disorders, deoxynucleoside triphosphate (dNTP) metabolism, and the MT central dogma. Rare variant analysis identified SAMHD1 mutation carriers as having higher mtDNA-CN (beta = 0.23 SDs; 95% CI, 0.18-0.29; p=2.6 × 10-19), a potential therapeutic target for patients with mtDNA depletion disorders, but at increased risk of breast cancer (OR = 1.91; 95% CI, 1.52-2.40; p=2.7 × 10-8). Finally, Mendelian randomization analyses suggest a causal effect of low mtDNA-CN on dementia risk (OR = 1.94 per 1 SD decrease in mtDNA-CN; 95% CI, 1.55-2.32; p=7.5 × 10-4). Conclusions: Altogether, our genetic findings indicate that mtDNA-CN is a complex biomarker reflecting specific MT processes related to mtDNA regulation, and that these processes are causally related to human diseases. Funding: No funds supported this specific investigation. Awards and positions supporting authors include: Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award (MC, PM); CIHR Post-Doctoral Fellowship Award (RM); Wellcome Trust Grant number: 099313/B/12/A; Crasnow Travel Scholarship; Bongani Mayosi UCT-PHRI Scholarship 2019/2020 (TM); Wellcome Trust Health Research Board Irish Clinical Academic Training (ICAT) Programme Grant Number: 203930/B/16/Z (CJ); European Research Council COSIP Grant Number: 640580 (MO); E.J. Moran Campbell Internal Career Research Award (MP); CISCO Professorship in Integrated Health Systems and Canada Research Chair in Genetic and Molecular Epidemiology (GP).

Our cells are powered by small internal compartments known as mitochondria, which host several copies of their own 'mitochondrial' genome. Defects in these semi-autonomous structures are associated with a range of severe, and sometimes fatal conditions: easily checking the health of mitochondria through cheap, quick and non-invasive methods can therefore help to improve human health. Measuring the concentration of mitochondrial DNA molecules in our blood cells can help to estimate the number of mitochondrial genome copies per cell, which in turn act as a proxy for the health of the compartment. In fact, having lower or higher concentration of mitochondrial DNA molecules is associated with diseases such as cancer, stroke, or cardiac conditions. However, current approaches to assess this biomarker are time and resource-intensive; they also do not work well across people with different ancestries, who have slightly different versions of mitochondrial genomes. In response, Chong et al. developed a new method for estimating mitochondrial DNA concentration in blood samples. Called AutoMitoC, the automated pipeline is fast, easy to use, and can be used across ethnicities. Applying this method to nearly 400,000 individuals highlighted 71 genetic regions for which slight sequence differences were associated with changes in mitochondrial DNA concentration. Further investigation revealed that these regions contained genes that help to build, maintain, and organize mitochondrial DNA. In addition, the analyses yield preliminary evidence showing that lower concentration of mitochondrial DNA may be linked to a higher risk of dementia. Overall, the work by Chong et al. demonstrates that AutoMitoC can be used to investigate how mitochondria are linked to health and disease in populations across the world, potentially paving the way for new therapeutic approaches.

Sustainable Use of Marble Waste in Industrial Production of Fired Clay Bricks and Its Employment for Treatment of Flue Gases.

In the current study, waste marble powder was utilized to produce lightweight fired clay bricks and in the treatment of flue gases. Marble waste powder used in clay bricks and flue gas treatment was collected from local marble processing plants, and its chemical composition was analyzed using energy-dispersive X-ray analysis and X-ray fluorescence. Clay bricks were produced in local fired clay brick kiln by partial replacement (10-40%) of clay with calcined and uncalcined waste marble powder. The temperature in the firing zone of the kiln was 1000-1100 °C. Clay brick properties such as compressive strength, bulk density, porosity, and water absorption were analyzed. Results show that the porosity of clay bricks increases with an increase in marble waste percentage, and due to an increase in porosity, water absorption of clay bricks also increases, while compressive strength and bulk density decrease. Clay bricks with 10% uncalcined marble waste and 20% calcined marble waste satisfy the required Turkish and European compressive strength standard. Marble waste decreases the concentration of sulfur dioxide and particulate matter in flue gases. There is up to 43 and 65% reduction in the concentration of sulfur dioxide and particulate matters, respectively, in flue gases, after treatment with marble waste. The addition of marble waste to clay bricks is an effective and economical solution for waste marble powder management. Furthermore, it can be used for the treatment of flue gases from brick kilns before its addition to clay bricks.

Pharmacological evaluation and in-silico modeling study of compounds isolated from Ziziphus oxyphylla.

Medicines derived from plants are preferred over synthetic therapeutic agents in treating different diseases. Ziziphus oxyphylla (a member of Rhamnaceae family) is a medicinal plant used as a remedy of different diseases in Greek and Ayurveda medical systems. Z. oxyphylla roots were shade dried and then subjected to extraction of bioactive compounds using different solvent systems and silica gel. From ethyl acetate fraction, three compounds viz., p-coumaric acid (V), 3,4-dimethoxy benzoic acid (VI), and 4-heptyloxy benzoic acid (VII) were isolated in pure form. The selection of ethyl acetate fraction for isolation was based on HPLC profiling of crude extract and different fractions. These compounds were characterized by different spectroscopic techniques and evaluated for their in vitro antioxidant, anticholinesterase, α-glucosidase, and α-amylase inhibitory potentials. To find out possible binding interactions of V with AChE and BChE crystals, in-silico docking studies were also carried out. Compound V showed maximum scavenging capabilities of DPPH and ABTS free radicals with IC50 values of 69 and 62 µg/mL respectively. Excellent percent inhibition (83.4 ± 0.5% at highest concentration 1000 µg/mL) of acetylcholinesterase (AChE) was exhibited by compound V (IC50 = 80 µg/mL); whereas, for the mentioned concentration, 83.2 ± 1.1% inhibition (IC50 = 90 µg/mL) of butyrylcholinesterase (BChE) was observed as well. The compound VI exhibited highest % inhibition against α-glucosidase (IC50 = 84 µg/mL) whereas α-amylase was more potently inhibited by compound V (% inhibition = 86.8 % and IC50 = 85 µg/mL). Docking scores of -1.391 Kcal/mol (BChE) and -6.253 Kcal/mol (AChE) were recorded using molecular docking software. Compound V exhibited strong free radical scavenging and anticholinesterase potentials suggesting that it can be effectively used to treat oxidative stress and dementia in human.

Micropropagation and Production of Health Promoting Lignans in Linum usitatissimum.

Linum usitatissimum commonly known as flax or linseed is an important medicinal plant, produces medicinally potent lignans, used in the treatment of several human diseases. Lignans limited production in the natural plants does not meet the increasing market demand. This study was conducted to establish an easy and rapid method for the in vitro micropropagation and production of potent lignans and antioxidant secondary metabolites in linseed. The results indicated that hypocotyl explants under the effects of thidiazuron (TDZ: 0.5 mg/L) + kinetin (Kn: 0.5 mg/L) in the basal growth media, resulted in the optimal shoot organogenesis parameters (shoot induction frequency: 86.87%, number of shoots: 6.3 ± 0.36 and shoots length: 6.5 ± 0.54 cm), in 4 weeks. Further, TDZ supplementation in the culture media efficiently activated the antioxidant system in the in vitro raised shoots, wherein maximum production of total phenolic content, TPC (34.33 ± 0.20 mg of GAE/g DW); total flavonoid content, TFC (8.99 ± 0.02 mg of QE/g DW); DPPH free radical scavenging activity (92.7 ± 1.32%); phenylalanine ammonia-lyase activity, PAL (8.99 ± 0.02 U/g FW); and superoxide dismutase expression, SOD (3.62 ± 0.01 nM/min/mg FW) were observed in the shoot cultures raised in presence of TDZ: 0.5 mg/L + Kn: 0.5 mg/L. Nonetheless, considerable levels of pharmacologically active lignans such as secoisolariciresinol (SECO: 23.13-37.10 mg/g DW), secoisolariciresinol diglucoside (SDG: 3.32-3.86 mg/g DW) and anhydrosecoisolariciresinol diglucoside (ANHSECO: 5.15-7.94 mg/g DW) were accumulated in the regenerated shoots. This protocol can be scaled up for the commercial production of linseed to meet the market demands for lignans.

Toxicological, anticholinesterase, antilipidemic, antidiabetic and antioxidant potentials of Grewia optiva Drummond ex Burret extracts.

Background In this study, Grewia optiva Drummond ex Burret root extracts were assessed for use as a remedy for oxidative stress, diabetes mellitus and neurological disorders. Methods The antioxidative potentials of the extracts were determined using DPPH and ABTS assays, whereas their enzyme inhibitory potentials were determined against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase and α-amylase. In the in vivo experiments, methanol extract was orally administered to mice (n = 5) at four doses of 200, 300, 400 and 500 mg kg-1 for 30 days and its effect on glucose, triglycerides, total cholesterol, etc. were investigated. Results The highest free radical scavenging activities against DPPH and ABTS radicals were recorded for the methanol and ethyl acetate extracts, and their respective IC50 values were 75 and 88 µg/mL. In addition, these two fractions were highly active in inhibiting AChE and BChE, with IC50 values of 120 and 185 µg/mL, respectively. Moderate inhibition (µg/mL) was recorded against α-glucosidase (69.02 ± 1.02 and 64.29 ± 2.41) and α-amylase (65.12 ± 2.02 and 63.29 ± 1.41) and these were comparable to the inhibitory activities exhibited by the standard, acarbose. All the extracts showed high phenolic and flavonoid contents, which correlated with their antioxidant, anticholinesterase, α-glucosidase and α-amylase activities. The phenolic compounds in the crude extract and fractions were determined using the standard HPLC method and bioactive compounds, namely, morin, ellagic acid, kaempferol-3-(p-coumaroyl-diglucoside)-7-glucoside, apigenin-7-O-rutinoside, quercetin-3-(caffeoyl-diglucoside)-7-glucoside, etc., which were detected at various retention times. Significant decrease in cholesterol, triglyceride and blood glucose levels were observed. Conclusion G. optiva is a good source of antioxidants and other phytochemicals, some of which possess anticholinesterase, anti-glucosidase, and anti-amylase activities, and can be used to treat different health conditions such as oxidative stress, neurological disorders, and diabetes mellitus.

Risk of Cardiovascular Events in Patients With Type 2 Diabetes and Metabolic Dyslipidemia Without Prevalent Atherosclerotic Cardiovascular Disease.

BACKGROUND: The relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and risk of incident atherosclerotic cardiovascular disease events among patients with diabetes and metabolic dyslipidemia has not been well described. METHODS: We conducted an observational cohort study of statin-treated adults (ages 21-90 years) with type 2 diabetes without established atherosclerotic cardiovascular disease (as of January 1, 2006) who had metabolic dyslipidemia (elevated triglycerides ≥150 mg/dL and low high-density lipoprotein cholesterol, <50 mg/dL [women] and <40 mg/dL [men]). All subjects were members of Kaiser Permanente Northern California, an integrated health care delivery system. Adjusted multivariable Cox models were specified to estimate hazard ratios (HRs) for incident atherosclerotic cardiovascular disease events by achieved LDL-C levels (<50, 50-<70, 70-<100, and ≥100 mg/dL). Incident atherosclerotic cardiovascular disease events were defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through December 31, 2013. RESULTS: A total of 19,095 individuals met the selection criteria. Mean age was 63.4 years, 53.5% were women, and the mean follow-up was 5.9 years. Unadjusted rates of atherosclerotic cardiovascular disease events were not significantly different across specified LDL-C categories. In models adjusted for demographics and clinical characteristics, the risk was significantly lower with decreasing achieved LDL-C levels (P <0.0001 for trend). Relative to achieved LDL-C ≥100 mg/dL, LDL-C <50 mg/dL had an hazard ratio of 0.66 (95% confidence interval [CI] 0.52-0.82). CONCLUSION: In a large, contemporary cohort of statin-treated patients with type 2 diabetes and metabolic dyslipidemia without established atherosclerotic cardiovascular disease, lower achieved LDL-C levels were associated with a monotonically lower risk of incident atherosclerotic cardiovascular disease events. The benefits of achieving very-low LDL-C (<50 mg/dL) in this population requires further evaluation in prospective interventional studies.

Isolation, pharmacological evaluation and molecular docking studies of bioactive compounds from Grewia optiva.

BACKGROUND: Traditionally, Grewia optiva is widely used for the treatment of many diseases like dysentery, fever, typhoid, diarrhea, eczema, smallpox, malaria and cough. METHODS: Shade-dried roots of G. optiva were extracted with methanol. Based on HPLC results, chloroform and ethyl acetate fractions were subjected to silica column isolation and four compounds: glutaric acid (V), 3,5 dihydroxy phenyl acrylic acid (VI), (2,5 dihydroxy phenyl) 3',6',8'-trihydroxyl-4H chromen-4'-one (VII) and hexanedioic acid (VIII) were isolated in pure form. Ellman's assay was used to determine the anticholinesterase potential of isolated compounds while their antioxidant potential was estimated by DPPH and ABTS scavenging assays. RESULTS: Amongst the isolated compounds, VI and VII exhibited excellent percent inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (83.23±1.11, 82.72±2.20 and 82.11±2.11, 82.23±1.21, respectively, at 1000 µg/mL) with IC50 of 76, 90, 78 and 92 µg/mL, respectively. Highest percent radicals scavenging against DPPH and ABTS (87.41±1.20 and 86.13±2.31) with IC50 of 64 and 65 µg/mL, respectively, were observed for compound VII. Molecular docking studies also supported the binding of compound VI and VII with the target enzyme. The para-hydroxyl group of the phenolic moiety is formed hydrogen bonds with the active site water molecule and the side chain carbonyl and hydroxyl residues of enzyme. CONCLUSION: The isolated compounds inhibited the DPPH and ABTS-free radicals, and AChE and BChE enzymes. It was concluded that these compounds could be used in relieving the oxidative stress and pathological symptoms associated with excessive hydrolysis of acetyl and butyryl choline. The results of the study were supported by docking studies for compounds VI and VII.

Biological and biochemical characteristics of male reproductive system, serum metabolites and carcass quality of Japanese quails by the supplementation of Pinus ponderosa leaves and α-tocopherol acetate.

The aim of the current study was to evaluate the effect of dietary supplementation of Pinus ponderosa leaves (pine leaves) and α-tocopherol acetate (vitamin E) powder on male reproductive system, serum metabolites and carcass characteristics of Japanese quails. A total of 360-day-old male quails were purchased from the open market and kept at poultry shed for ninety-four days. After ten days of adaptation, all quails were randomly assigned into 4 groups, control (IC); supplemented with α-tocopherol acetate (IE) at the rate of 150 mg/L; Pinus ponderosa leaves (IP) at the rate of 150 mg/L; and 70 mg α-tocopherol acetate and 70 mg Pinus ponderosa leaves (IEP). Pinus ponderosa leaves and α-tocopherol acetate supplementation had not significantly (p > .05) effected on final body weight gain, feed intake and feed conversion ratio of quails. The high-density lipoprotein cholesterol (HDLC) and total cholesterol (TC) were significantly (p > .05) affected by IE and IP groups as compared to IC and IEP groups. Triglyceride (TG), glutathione peroxidase (GPx) and superoxide dismutase (SOD) significantly (p < .05) increased in all treatment groups except for the IC group. Aspartate transaminase (AST) significantly (p > .05) decreased in treatment groups as compared to control group. Overall, the mineral levels significantly (p < .05) increased in treatment groups as compared to control. Cloacal gland index values, the quantity of foam production and testis weight were significantly (p < .05) increased in treatment groups. It was concluded that the supplementation of Pinus ponderosa leaves and α-tocopherol acetate improved the testis weight, foam production, serum antioxidant enzymes and mineral level especially zinc in Japanese quail considered an indicative characteristic of higher sperm production rate and improved sexual activity. Further, higher gametogenesis rate, sperm production or reproductive behaviour including different hormonal level will be analysed in future study.

Biosynthesis of anti-leishmanial natural products in callus cultures of Artemisia scoparia.

Clinically, available synthetic chemotherapeutics in the treatment for leishmaniasis are associated with serious complications, such as toxicity and emergence of resistance. Natural products from plants can provide better remedies against the Leishmania parasite and can possibly minimize the associated side effects. In this study, various extracts of the callus cultures of Artimisia scoparia established in response to different plant growth regulators (PGRs) were evaluated for their anti-leishmanial effects against Leishmania tropica promastigotes, followed by an investigation of the possible mechanism of action through reactive apoptosis assay using fluorescent microscopy. Amongst the different callus extracts, higher anti-leishmanial activity (IC50:19.13 µg/mL) was observed in the callus raised in-vitro in the presence of 6-Benzylaminopurine (BA) plus 2,4-Dichlorophenoxyacetic Acid (2,4-D) at the concentration of 1.5 mg/L, each. Further, the results of apoptosis assay showed a large number of early-stage apoptotic (EA) and late-stage apoptotic (LA) cells in the Leishmania under the effect of callus extract grown in-vitro at BA plus 2,4-D. For the determination of the potent natural products in the callus extracts responsible for the anti-leishmanial activity, extracts were subjected to Gas chromatography-mass spectrometry (GC-MS) for the metabolite analysis. Nonetheless, higher levels of the metabolites, such as nerolidol (22%), pelletierine (18%), aspidin (15%) and ascaridole (11%) were detected in the callus grown in vitro at BA plus 2,4-D (1.5 mg/L, each). This protocol determines a novel method of production of anti-leishmanial natural products through callus cultures of A. scoparia, a medicinal plant.

Risk of Incident Atherosclerotic Cardiovascular DiseaseEvents by Achieved Atherogenic Lipid Levels Among62,428 Statin-Treated Individuals With Diabetes Mellitus.

The relevance of low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) goals for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among patients with diabetes was assessed. This retrospective cohort study included patients with type 2 diabetes, age 21 to 90years, taking statins, with no history of ASCVD as of January 1, 2006, in Kaiser Permanente Northern California, an integrated healthcare delivery system. Multivariate cox models were utilized to estimate hazard ratios (HRs) for incident ASCVD events by achieved LDL-C and non-HDL-C levels with adjustment for potential confounders. Incident ASCVD events were defined as a composite of myocardial infarction, ischemic stroke, or coronary heart disease death. A cohort of 62,428 patients, with mean age of 64.1years, 46.9% women, and mean follow-up of 6.0 years, was identified. After adjustment, the risk of incident ASCVD for these statin-treated patients was monotonically lower with decreasing achieved LDL-C levels (p<0.0001 for trend) and non-HDL-C levels (p <0.0001 for trend). Relative to achieved LDL-C ≥130 mg/dl, LDL-C <50 mg/dl had HR = 0.58 (95% confidence interval 0.49 to 0.69). Relative to achieved non-HDL-C ≥160mg/dl, non-HDL-C <80 mg/dl had HR = 0.59 (95% confidence interval 0.51 to 0.68). In a large cohort of statin-treated diabetic patients without ASCVD, a monotonically lower risk of incident ASCVD events was associated with lower achieved lipid levels. These findings support the use of LDL-C ornon-HDL-C treatment goals for ASCVD primary prevention in diabetic patients.

Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011-2012.

BACKGROUND: The 2013 American College of Cardiology/American Heart Association Cholesterol Management Guideline identifies 4 statin-eligible groups: (1) known atherosclerotic cardiovascular disease (ASCVD) aged ≥21 years, (2) low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL (4.9 mmol/L) aged ≥21 years, (3) diabetes mellitus aged 40 to 75 years with LDL-C 70 to 189 mg/dL (1.8-4.9 mmol/L), or (4) ≥7.5% 10-year ASCVD risk aged 40 to 75 years with LDL-C 70 to 189 mg/dL (1.8-4.9 mmol/L). OBJECTIVES: We examined the number of statin-eligible US adults, statin use, LDL-C goal attainment, and adherence to lifestyle management. METHODS: We identified subjects from the US National Health and Nutrition Examination Survey 2011-2012 in the 4 statin-eligible groups, proportion on statin, proportion at recommended LDL-C levels using National Lipid Association goals (<70 mg/dL [1.8 mmol/L] for very high risk and <100 mg/dL [2.6 mmol/L] for others), and adherence to lifestyle measures. RESULTS: Of 5206 adults (representing 219 million), 1677 adults representing 62.6 million adults fit into 1 of the 4 statin-eligible groups. Statin use was 63.7% for the ASCVD, 61.4% for the LDL-C ≥ 190 mg/dL (4.9 mmol/L), 43.2% for the diabetes mellitus, and 27.2% for the 10-year risk ≥7.5% groups. Of those on statins with LDL-C measured, 79.7%, 98.0%, 42.3%, and 46.8% were not at LDL-C goal. Adherence to recommended <6% calories from saturated fat ranged from 3.3% to 6.4% and ≥40 minutes of physical activity ≥3 times a week from 54.7% to 65.1% across statin-eligible groups. CONCLUSION: Many US adults eligible to receive statins based on American College of Cardiology/American Heart Association guidelines are not taking statins, and LDL-C levels still remain suboptimal.

Comparative evaluation of efficacy and safety profile of rhubarb and α-keto analogs of essential amino acids supplementation in patients with diabetic nephropathy.

To determine the efficacy and safety profile of rhubarb and α-keto analogs of essential amino acids supplementation in patients of diabetic nephropathy (DN), we studied 96 patients of DN attending a tertiary care center of the North India. The patients were randomly divided into three equal interventional groups. Group I (control) that received conservative management along with placebo, Group II (rhubarb) that received conservative management along with rhubarb capsule (350 mg, thrice daily), and Group III [keto amino acid (KAA)] that received conservative management along with α-keto analogs of essential amino acids (600 mg, thrice daily). The treatment was continued for 12 weeks. Clinical and biochemical parameters were assessed at 0, 4, 8, and 12 weeks of treatment. A progressive improvement in clinical features and biochemical parameters was seen in all three groups after 12 weeks of treatment. The KAA group showed more marked improvement in clinical features as well as biochemical parameters compared to the rhubarb group. There was a reduction in blood glucose, blood urea, serum creatinine, and 24 h total urine protein. There was an increase in hemoglobin, 24 h total urine volume, and glomerular filtration rate. There was no statistical difference between the rhubarb and KAA groups with respect to side effects (P > 0.05). Our study suggests that KAA is more effective than rhubarb as add-on therapy with conservative management in patients of DN.

Detection of carcinogenic metals in kidney stones using ultraviolet laser-induced breakdown spectroscopy.

The UV single-pulsed (SP) laser-induced breakdown spectroscopy (LIBS) system was developed to detect the carcinogenic metals in human kidney stones extracted through the surgical operation. A neodymium yttrium aluminium garnet laser operating at 266 nm wavelength and 20 Hz repetition rate along with a spectrometer interfaced with an intensified CCD (ICCD) was applied for spectral analysis of kidney stones. The ICCD camera shutter was synchronized with the laser-trigger pulse and the effect of laser energy and delay time on LIBS signal intensity was investigated. The experimental parameters were optimized to obtain the LIBS plasma in local thermodynamic equilibrium. Laser energy was varied from 25 to 50 mJ in order to enhance the LIBS signal intensity and attain the best signal to noise ratio. The parametric dependence studies were important to improve the limit of detection of trace amounts of toxic elements present inside stones. The carcinogenic metals detected in kidney stones were chromium, cadmium, lead, zinc, phosphate, and vanadium. The results achieved from LIBS system were also compared with the inductively coupled plasma-mass spectrometry analysis and the concentration detected with both techniques was in very good agreement. The plasma parameters (electron temperature and density) for SP-LIBS system were also studied and their dependence on incident laser energy and delay time was investigated as well.

Sedative and anxiolytic effects of ethanolic extract of Calotropis gigantea (Asclepiadaceae) leaves.

OBJECTIVE: To evaluate possible anxiogenic activity, sedative property and anxiolytic potential of crude ethanolic extract of Calotropis gigantea leaves. METHODS: The anxiogenic activity of crude ethanolic extract of Calotropis gigantea leaves was evaluated using standard animal behavioral models, such as hole cross and open field; sedative property and anxiolytic potential were evaluated by conducting thiopental sodium induced sleeping time tests and elevated plus-maze test. RESULTS: The crude ethanolic extract exhibited a significant (P<0.05, P<0.001) decrease of motor activity and exploratory behavior in hole cross and open field tests. The extract also markedly increased both the number of visits to and time spent in the corners of the open field. The extract treated rats spent more time in the open arm of elevated plus-maze, showing its antianxiety activity. There was a decrease in the locomotor activity. CONCLUSIONS: The obtained results provide support for the use of this species in traditional medicine and warrant further investigation to isolate the specific components that are responsible for the sedative and anxiolytic effects. Components from this plant may have a great potential value as medicinal agents, as leads or model compounds for synthetic or semi synthetic structure modifications and optimization, and as neuropharmacological probes.

Salsola pollen as a predominant cause of respiratory allergies in Kuwait.

BACKGROUND: Respiratory allergies are common in Kuwait, and the role of certain allergens has been previously documented. OBJECTIVE: To evaluate the results of skin prick tests to a range of allergens that were considered relevant to the vegetation surveys and aerobiological studies performed in Kuwait. METHOD: New patients attending our center during August 2002 to February 2003 with asthma or allergic rhinitis underwent skin prick tests to a battery of allergens. RESULTS: A total of 451 patients aged 5 to 60 years (mean age, 29.5 years) were tested. Of these patients, 403 (89.4%) had a positive test result to at least one allergen and were considered allergic. A total of 76.7% of the allergic patients had a positive reaction to Salsola pollen, with a mean wheal diameter of 8.25 mm (median, 8 mm). Chenopodium album was positive in 57.6% and Bermuda grass was positive in 38.2% of the allergic cases. Indoor allergens seemed to play a lesser role than pollens: Dermatophagoides pteronyssinus was positive in only 37.5%, and American and German cockroaches were positive in 33.2% and 22.3%, respectively. All the allergens other than Salsola elicited a mean wheal diameter of less than 6.25 mm (median, < or = 6 mm). CONCLUSIONS: Indoor allergens seem to play a lesser role in respiratory allergies in Kuwait. Most allergic patients become sensitized to pollens; the strongest and most frequent reaction is from Salsola pollen. Salsola imbricata is found growing extensively in most areas of the country, flowering mainly in autumn, when the most common pollen is of the Chenopod-Amaranth type and when most patients with seasonal allergic rhinitis become symptomatic.