This study was undertaken to determine the hypoglycemic effect of Commiphora africana (family: Burseraceae) stem bark aqueous-ethanolic extract in normoglycemic Wistar rats. In one set of experiment, graded doses of C. africana stem bark aqueous extract (100, 200 and 400 mg/kg p.o) were separately administered to groups of fasted normal rats. The hypoglycemic effect of C. africana stem bark aqueous ethanolic extract was compared with that of M etformin (250 mg/kg) in fasted normal rats. Following treatment, relatively moderate to high doses of C. africana (100, 200 and 400 mg/kg p.o) produced a dose-dependent, significant reduction (p＜0.05) in blood glucose levels of fasted normal rats. Three doses of the extract (100, 200 and 400 mg/kg) were administered orally. A significant decrease in the blood glucose levels after 5 and 7 day of administration with the doses of 200mg/kg and 400mg/kg was observed when compared to control. As regards to the dose of 100mg/kg there was no any significant decreased in the blood glucose levels when compared to control. The Preliminary phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, steroids and saponins. The median lethal dose (LD50) in rats was calculated to be 3807.8 mg/kg body weight. In conclusion the aqueous ethanolic extract of Commiphora africana possesses hypoglycemic activity in normoglycemic rats.
Bidens pilosa, a member of the Asteraceae family, is one of the dominant medicinal plant species worldwide including Uganda. This study aimed at assessing both acute and sub-chronic toxicities of Bidens pilosa Leaves Extract (BPLE). Phytochemical tests were done on BPLE to detect the presence of secondary metabolites. In acute toxicity test, a single oral dose of BPLE (500-10,000 mg/kg) was used on each group of Wistar rats. For sub-chronic toxicity study, BPLE (200-800 mg/kg) and distilled water were orally administered daily for 28 days. Signs of toxicity were observed and rats sacrificed, blood and organs collected for biochemical and histological studies. The BPLE was found to contain tannins, flavonoids, phlobatannins, terpenoids and cardiac glycosides. No mortality was recorded during the studies in rats. There was a general reduction in mean percentage body weight gain of test rats compared with control; statistically significant (p<0.05) between 400 mg/kg and control and between 400 and 800 mg/kg. Significant increments in mean relative organ weight of the heart occurred between control and 400 mg/kg groups. There were significant (p<0.05) increases in the serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma Glutamyl Transpeptidase (GGT) enzymes at dose of 800 mg/kg and of cardiac Creatine Kinase (CK- MB) at all three doses when compared with the control. Light micrograph of the liver, kidney and heart tissues at 400 magnifications appeared normal with no changes. It can be concluded that BPLE from the Rift Valley Region of Western Uganda contains secondary metabolites and has high index of safety.
This study was undertaken to evaluate the hypoglycemic effect of aqueous-ethanolic stem bark extract of Commiphora african on blood glucose levels of alloxan-induced diabetes rats. Three doses of the extract (100, 200 and 400 mg/kg) were administered p. o. There was a significant decreased in the blood glucose levels after 1 day of treatment with the dose of 400 mg/kg. Also after 5 and 7 days of treatment there was a significant decrease in the blood glucose levels with the doses of 200 and 400 mg/kg when compared to control. As regards to the dose of 100 mg/kg there was no any significant decreased in the blood glucose levels when compared to control. The Preliminary phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, steroids and saponins. The median lethal dose (LD50) in rats was calculated to be 3.8078 mg/kg body weight. In conclusion the aqueous ethanolic stem bark extract of Commiphora Africana possess anti-diabetic effect in alloxan- induced in diabetic rats.
Hyperglycemia is a common feature of diabetes mellitus. It results from a decrease in glucose utilization by the liver and peripheral tissues and an increase in hepatic glucose production. Glucose phosphorylation by glucokinase is an initial event in glucose metabolism by the liver. However, glucokinase gene expression is very low in diabetic animals. Hepatic GCK is a key enzyme in glucose homeostasis and, as such, is a potential target for treatment strategies of diabetes. The present day study investigated the effect of co- administration of folic acid and magnesium on GCK activity. Thirty wistar male rats were divided into six groups of five each. Diabetic groups received 20 and 500 mg/kg folic acid and /or magnesium chloride, separarately or in combination. Diabetic control and normal control received 0.9% saline for 4 weeks. It was found that during combined exposure of folic acid and magnesium, the adverse effects of the diabetes induced by STZ was less pronounced in the group that had FA+ Mg than their individual effects. This suggests the synergistic beneficial effects of folic acid and Magnesium against STZ-induced diabetes in Wistar Rats. Investigations of the hepatic glucokinase concentration by Real-Time PCR showed a decreased in GCK concentration in diabetic control rats. GCK activity increased significantly (p<0.05) in group treated with FA+Mg. These results indicated that FA+Mg co- administration may probably exhibit a significant potential as a hypoglycemic agent perhaps via its ability to enhance GCK gene expression and its activity.
This aim of this study was to evaluate the hypoglycemic effect of residual aqueous portion of hydromethanolic leaves extract of indigofera pulchra on blood glucose levels of alloxan-induced diabetes rats. Three doses of the extract (250,500 and 1000 mg/kg) were administered intraperitoneally. After 2, 4 and 6 h of extract administration there was no significant change in the blood glucose levels in all the three doses of the extract administered when compared to the control. Also after 8 and 24 hours of extract administration there was a significant (p＜0.05) decrease in the blood glucose levels with the dose of 1000mg/kg the extract administered. In regard to the dose of 500mg/kg there was a significant decrease (p＜0.05) after 24 h of extract administration. In relation to the reference drug there was a significant decrease (p＜0.05) after 4, 8 and 24 h of administration when compared to control. The Preliminary phytochemical screening revealed the presence of alkaloids, tannins, flavonoids and saponins. The median lethal dose (LD50) in rats was calculated to be 2,154 mg/kg body weight. In conclusion the residual aqueous portion of hydromethanolic leaves extract of Indigofera pulchra possess anti-diabetic effect in alloxan-induced in diabetic rats.
This study was undertaken to determine the hypoglycemic effect of Moringa oleifera (family: Moringaceae) ethanolic extract in normal (normoglycemic) and STZ induced diabetic Wistar rats. In one set of experiment, graded doses of the leaves extract (250 and 500 mg/kg i.p.) were separately administered to groups of fasted normal and fasted STZ diabetic rats. The hypoglycemic effect of the ethanolic leaves extract was compared with that of insulin 6 i.u/kg in fasted normal and STZ diabetic rats. Following treatment, relatively moderate to high doses of Moringa oleifera (250 and 500 mg/kg i.p.) produced a dose-dependent, significant reduction (p<0.05) in blood glucose levels of fasted STZ diabetic rats only. A significant decrease in the blood glucose levels after 1-7 h of administration with the doses of 250 and 500 mg/kg was observed in the STZ diabetic group when compared to control. As regards to the dose of 250 and 500 mg/kg for the fasted normal rats, there was significant increase in the blood glucose levels when compared to control. In conclusion the ethanolic extract of the leaves of Moringa oleifera possesses hypoglycemic activity in STZ induced diabetic Wistar rats only.
Background: Diabetes mellitus (DM) is a global public health problem with increasing prevalence. It is a chronic disorder characterized by hyperglycemia and the late development of vascular and neuropathic complications. This work was designed to study the effects of folic acid and magnesium co- administration on some haematological parameters in STZ induced diabetic rats. Methodology: Healthy albino rats weighing between 150g and 200g were used. The rats were randomly allotted into six groups, each containing five albino rats respectively. Five of the groups (II, III IV V and VI) were induced with diabetes by single intraperitoneal (i.p) injection of freshly prepared in 0.1 mol/L citrate buffered solution (pH 4.5) of streptozotocin (Sigma Aldrich, St. Louis, MO, USA) at a dose of 60 mg/kg body weight. Control (vehicle) rats were injected with equal volume of 0.1 mol/L citrate buffer. Four days after STZ injection, diabetes induction was confirmed by measuring fasting blood glucose level in a tail vein blood samples using ACCU-CHEK compact plus glucometer (Roche, France). Rats with glucose level of 200 mg/dl or higher were considered as diabetic. After the induction of diabetes the rats were treated using the FA and Mg separately and in combination respectively according to group daily, whereas, the other group (I) was not given any treatment and this served as the normal control, providing a baseline data. Results: The results indicated that oral supplementation of folic acid (20 mg/kg b.w. /day) and MgCl2 (500/kg b.w. /day) separately or in combination for 4 weeks of treatment exhibited significant alterations in the haematological parameters in STZ-induced-type-1 diabetic; the diabetic rats showed marked reduction in packed cell volume (PCV), haemoglobin (Hb) content, red blood cell (RBC) count, mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and an increase in the platelet count. Conclusion: These anomalies were all ameliorated to about normal values after four weeks of treatment with FA+Mg. This suggests the synergistic beneficial effects of folic acid and Magnesium against STZ-induced diabetes in Wistar Rats.
23Nov 2016 EFFECTS OF ADMINISTRATION OF ETHANOLIC EXTRACT OF GANODERMA LUCIDUM ON ARTERIAL BLOOD PRESSURE OF NORMOTENSIVE CATS. A.D.T. Goji , J.A. Tende , D.S. Amaza and I. Ezekiel. Department of Human Physiology, Faculty of Medicine, Kaduna State University, Nigeria. Department of Human Physiology, Faculty of Medicine, Ahmadu Bello University Zaria, Nigeria. Department of Anatomy, Faculty of Medicine, Kaduna State University, Nigeria. Department of Biological Sciences, Faculty of Pure and Applied Sciences, Federal University Wukari, Nigeria.
This work was designed to study the effects of FA+ Mg (folic acid and magnesium) co-administration on blood glucose levels of STZ (streptozotocin) induced diabetic rats.Healthy albino rats weighing between 150 g and 200 g were used.The rats were randomly allotted into six groups, each containing five albino rats respectively.Five of the groups ( II, III, IV, V and VI) were induced with diabetes by the by i.p. (intraperitoneal) injection of freshly prepared in 0.1 mol/L citrate buffered solution (pH 4.5) of streptozotocin (Sigma Aldrich, St. Louis, MO, USA) at a dose of 60 mg/kg body weight.Control (vehicle) rats were injected with equal volume of 0.1 mol/L citrate buffer.Four days after STZ injection, diabetes induction was confirmed by measuring fasting blood glucose level in a tail vein blood samples using ACCU-CHEK compact plus glucometer (Roche, France).Rats with glucose level of 200 mg/dl or higher were considered as diabetic.After the induction of diabetes, the rats were treated using the folic acid and magnesium separately and in combination respectively according to group daily, whereas, the other group (a) was not given any treatment and this served as the normal control, providing a baseline data.Blood samples were collected from the rat tail vein weekly for a period of four weeks.Results obtained from the study showed that FA+ Mg administered conjointly lowered blood glucose levels after 4 weeks of treatment when compared to diabetic control, significantly (P < 0.05).The action of the co-administration of folic acid and magnesium on blood glucose in diabetic rats was similar to that of Insulin (6 IU/mL), a potent hypoglycaemic agent.Oral supplementation of folic acid (20 mg/kg b.w./day) and MgCl 2 (500/kg b.w./day) separately or in combination for 4 weeks of treatment exhibited differential protective response in lowering the blood glucose levels following treatments.It was also found that during combined exposure of folic acid and magnesium, the adverse effects of the diabetes induced by STZ were less pronounced in the group that had FA+ Mg than their individual effects.This suggests the synergistic beneficial effects of folic acid and Magnesium against STZ-induced diabetes in Wistar Rats.
Indigofera pulchra is used traditionally as prophylactic against snake-bite, treatment of infected wounds and as anti-inflammatory. In this study, the behavioural effects of hydromethanolic of the aerial part extracts of Indigofera pulchra were investigated in mice. The results revealed that the extract significantly (p＜0.05) prolonged the onset and reduced the duration of sleep at the dose tested (200mg/kg). The extract significantly (p＜0.05) increased exploratory activity at the dose tested (400mg/kg). It produced no significantly motor coordination deficits in mice at the doses tested (100, 200 and 400mg/kg). The intraperitoneal median lethal dose in mice was 2,154 mg/kg while the preliminary phytochemical screening revealed the presence of tannins, saponins, steroids and flavonoids. This result suggests that hydromethanolic extract of Indigofera pulchra might contains biologically active principles that are stimulative in nature and lend pharmacological credence to the ethnomedical use of the plant.
'/%3e%3cpath fill='%23c09300' stroke-width='1.074' d='m453.16 315.06 9.613 43.755-3.158 3.155-3.3-2.439-5.451-39.018 2.296 39.018-3.157 4.016-3.157-4.016 2.296-39.018-5.45 39.018-3.303 2.44-3.154-3.156 9.611-43.755h6.314z'/%3e%3cg id='b' fill='none' stroke-linejoin='round' stroke-width='1.27'%3e%3cpath fill='%23fff' stroke-width='1.189' d='m428.48 295.84-19.08 67.705 26.255 4.018 11.188-50.924-18.363-20.8z'/%3e%3cpath d='m422.17 318.94 2.296 5.593 12.405-11.848'/%3e%3cpath d='m430.76 304.92 2.596 24.346 7.89-10.328m-3.156 4.012 4.31 14.875m1.69-5.465-8.718 13.241m2.72 13.216-2.791-13.198-2.436-13.423-5.84 7.91-2.562-9.12-8.174 8.385 4.157 15.25 5.738-9.434 3.155 9.612 5.89-9.162'/%3e%3cpath d='m414.99 361.97 5.3-7.444 3.452 11.457 4.735-8.032 3.157 9.614'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='matrix(-1 0 0 1 900 0)'/%3e%3cg stroke-linecap='round' stroke-linejoin='round' stroke-width='1.27'%3e%3cpath stroke-width='2.378' d='M450 393.81c19.943 0 39.024-1.578 50.213-4.734 4.735-.859 4.735-3.298 4.735-6.455 4.736-1.578 2.295-7.17 5.595-7.17-3.3.862-4.016-5.595-8.033-4.732 0-5.597-5.596-6.313-10.33-4.738-9.47 3.158-26.255 3.875-42.18 3.875-15.924-.717-32.567-.717-42.18-3.875-4.733-1.575-10.326-.859-10.326 4.738-4.018-.863-4.736 5.594-8.034 4.731 3.299 0 .86 5.593 5.594 7.17 0 3.158 0 5.597 4.878 6.456 11.045 3.156 30.128 4.734 50.068 4.734z'/%3e%3cpath d='M422.89 363.54c6.454.861 13.628 1.578 19.225.861 3.153 0 5.45 5.45-.863 6.313-5.593.715-14.345 0-19.08-.862-4.017-.718-12.768-2.295-18.364-3.876-5.594-2.436-1.576-7.168 1.578-6.452 4.879 1.577 11.192 3.157 17.505 4.016zm54.23 0c-6.457.861-13.628 1.578-19.081.861-3.3 0-5.596 5.45.717 6.313 5.596.715 14.347 0 19.078-.862 4.019-.718 12.77-2.295 18.364-3.876 5.597-2.436 1.58-7.168-1.577-6.452-4.878 1.577-11.19 3.157-17.501 4.016z'/%3e%3cpath d='M403.09 360.39c-4.877-.861-7.172 4.732-5.593 7.887.717-1.578 4.017-1.578 4.735-3.155.858-2.437-.718-2.437.858-4.732zm19.08 14.67c0-3.153 3.155-2.765 3.155-5.921 0-1.577-.86-4.018-2.437-4.018-1.579 0-3.158 1.578-3.158 3.156-.718 3.157 2.44 3.63 2.44 6.783zm22.71-9.08c4.73 0 4.262 6.314 1.966 9.47 0-2.295-4.017-3.156-4.017-4.732 0-2.442 3.626-2.442 2.051-4.738zm52.03-5.59c4.878-.861 7.174 4.732 5.595 7.887-.718-1.578-4.017-1.578-4.734-3.155-.86-2.437.718-2.437-.86-4.732zm-19.08 14.67c0-3.153-3.153-2.765-3.153-5.921 0-1.577.86-4.018 2.438-4.018 1.577 0 3.156 1.578 3.156 3.156.718 3.157-2.44 3.63-2.44 6.783zm-22.71-9.08c-4.732 0-4.263 6.314-1.967 9.47 0-2.295 4.015-3.156 4.015-4.732.001-2.442-3.626-2.442-2.048-4.738z'/%3e%3cpath stroke-width='.891' d='M404.67 361.97c1.58 0 4.018.718 4.735 1.577l-4.74-1.58zm7.88 2.44c.862 0 4.018.716 5.596 1.575l-5.6-1.58zm28.7 3.15c-1.578 0-4.734 0-5.593.715l5.59-.72zm-8.75 0c-.859-.862-4.016-.862-5.593 0h5.59zm62.84-5.59c-1.578 0-3.875.718-4.735 1.577l4.735-1.577zm-7.89 2.44c-.86 0-4.017.716-5.595 1.575l5.6-1.58zm-28.7 3.15c1.58 0 4.735 0 5.595.715l-5.6-.72zm8.75 0c.86-.862 4.018-.862 5.595 0h-5.6z'/%3e%3cg fill='%23c09300' stroke='none'%3e%3cpath d='M403.34 374.58c-.534-.102-.815-.525-.68-1.025.164-.609.651-.957 1.112-.794.294.104.83.645.832.839.003.222-.28.752-.402.754-.053 0-.135.046-.182.102-.1.118-.413.175-.68.124zm54.93 3.92c-.199-.074-.515-.518-.515-.724.002-.387.574-1.018.929-1.021.175-.001.655.248.834.434.325.338.254.893-.154 1.208-.201.155-.8.212-1.094.103zm.36 2.48c-.42-.142-.574-.348-.608-.814-.036-.485.012-.56.525-.84l.365-.2.347.155c.48.214.693.445.71.767.018.348-.24.704-.64.883-.352.158-.373.16-.699.05z'/%3e%3cpath d='M407.75 370.09c-.346-.01-.821.307-1.094.469-.649.152-1.404.55-2.031.125-.617-.191-1.438-.04-1.531.718.158.652 1.071 1.025 1.625.594.41-.537 1.531-.853 1.656.063-.457.692-.405 1.609-.781 2.344-.061.457-.252.892-.5 1.28-.462.047-.954-.007-1.344.282-.626.034-1.265.345-1.625.875-.403.578-.789 1.165-.906 1.875.107.725.937.933 1.562.969.667.183 1.335.424 2 .625 1.086.243 2.102.635 3.188.875 1.584.477 3.248.697 4.844 1.125.167.055.324.104.5.125.662.137 1.007-.583 1.062-1.125.329-1.16.58-2.34.906-3.5.225-.466.497-1.517-.406-1.281-.515.308-.952.773-1.594.812-.874.05-.375.945-.031 1.313.076.587-.11 1.288-.5 1.75-.52.33-1.172-.057-1.719-.188-.574.01-1.723-.283-1.187-1.062.19-.577.207-1.209.437-1.782.294-.614.336-1.285.469-1.937-.361-.777-.979.256-1.469.344-.338.234-1.605.334-.937.937.575.437.134 1.197.03 1.75-.036.77-.837.954-1.468.781-.628-.03-1.501-.497-.969-1.187.121-.575.322-1.14.438-1.719.237-.698.437-1.363.687-2.062a5.78 5.78 0 0 1 .625-1.75c.018-.686.478-1.276.47-1.97-.048-.338-.2-.461-.407-.468zm-3.594 7.25a.353.353 0 0 1 .219.031c.25.106.257.31 0 .531-.112.097-.24.191-.281.188-.468-.04-.606-.11-.625-.281-.017-.151.03-.195.343-.344a1.45 1.45 0 0 1 .344-.125zm-1.036 5.02c-.496-.466-.416-.806.317-1.353.314-.234.505-.208.863.12.553.504.575.823.087 1.255-.24.213-.346.257-.627.26-.293.003-.376-.034-.64-.282zm3.05.92a.86.86 0 0 1-.623-1.088c.129-.434.203-.477.84-.483.716-.007.854.112.861.741.004.355-.023.437-.2.6-.207.193-.605.297-.878.23zm89.11.08c-.227-.189-.273-.274-.275-.515-.003-.41.233-.712.746-.944.682-.308.96-.266 1.216.186.342.601.325.847-.084 1.252-.225.224-.268.237-.785.242-.507.003-.565-.01-.818-.221zm-85.06 1.15c-.364-.097-.552-.37-.557-.807-.004-.334.02-.387.253-.57.152-.118.39-.22.579-.245.267-.037.364-.013.58.138.55.387.667.77.348 1.14-.34.397-.662.488-1.203.344zm21.92.98c-.08-.1-.26-.16-.278-.287.032-.555.059-1.117.236-1.648.096-.523.012-1.07.194-1.579.187-.927.187-1.882.402-2.803.01-.475.055-.95.193-1.406.157-.722.013-1.476.226-2.19-.023-.267.285-.983.556-.559.394.577.912 1.045 1.421 1.516.438.252.036.624-.266.75-.416.163-.517.62-.487 1.022-.058.414-.225.806-.242 1.23-.087.622-.07 1.254-.151 1.876-.182.609-.113 1.26-.173 1.888.008.398-.182.76-.156 1.16-.048.406-.066.894-.407 1.172-.329.166-.804.138-1.068-.142zm29.7-9.8c-.482.365-.914.795-1.344 1.219-.592.449.487.71.625 1.094.157.586.148 1.21.188 1.812.179.552.258 1.138.218 1.719-.051.622-.863.491-1.218.844-.492.207-.688.69-1.063 1.03-.246.484-.312 1.077-.344 1.626.036.448-.302.95 0 1.344.04.055.086.132.125.187.102.145.343.03.5.063.504-.029 1.029.047 1.5-.157 1.21-.209 2.432-.226 3.657-.28.749.023 1.47-.238 2.218-.22.587.13.851-.506.844-.968-.332-.654-.045-1.429-.312-2.094-.235-.673-.143-1.428-.25-2.125-.015-.549-.711-.752-1.063-.344-.341.345-.893.414-1.156.844-.297.602.627.603.781 1.062.176.465.118.98.156 1.47.115.592-.529.625-.937.687-.537.2-1.29.336-1.594-.313-.19-.48-.165-.993-.219-1.5-.013-.892-.227-1.768-.28-2.656-.052-1.097-.242-2.187-.313-3.281-.01-.456-.071-1.198-.72-1.063zm-.625 8.25.313.031.03.375.032.375-.406.125a3.28 3.28 0 0 1-.407.094 2.55 2.55 0 0 1-.187-.125c-.22-.159-.164-.385.125-.688.163-.17.239-.203.5-.187zm-29.965-9.28c-.38.135-.862.693-1.25.688-.88.062-.757.919-.125 1.218.083.26.005.588.031.875.123.79-.375 1.425-.281 2.22-.044.87-.307 1.717-.344 2.593-.247.903-.25 1.832-.406 2.75-.104.823-.7.533-1.219.312-.004-.356-.027-.705-.031-1.062.216-.817-.441-1.056-1.094-1.156-.686.065-1.023-.523-.875-1.125.295-.351 1.036-.254 1.5-.313.981.204.942-1.112.438-1.562-.345-.636-1.199-.91-1.438-1.563.096-.866-.48-1.732-1.187-2.156-1.089-.076-1.91.863-2.313 1.781-.452.131-.904.267-1.344.438-.709.177-1.72 1.407-.75 1.875.545.15 2.2.528 1.47 1.28-.413.708-1.202.72-1.907.532-.724 0-1.53-.352-1.5-1.187-.148-.75-.123-1.558-.469-2.25-.148-.84-1.1-.643-1.156.125-.733.534-.636 1.397-.125 2.03.319.73.003 1.578-.313 2.25-.19.876-1.155.906-1.843 1.188-.338.131-1.629-.078-1.156.657.753.265 1.652.505 2.437.312.823-.102 1.538-.665 1.938-1.375.552-.56 1.502-.267 2.218-.281.773-.002 1.563.542 2.313.187.217-.564 1.222-1.495 1.531-.53-.053.862.71 1.325 1.5 1.218.864-.05.544.61.531 1.125.057.934.66 1.425 1.438 1.812.265.072.545.048.812 0 .748-.235 1.554-.568 1.781-1.406.304-.68.311-1.45.532-2.156.177-1.13.406-2.26.437-3.406.276-1.039.197-2.136.406-3.188.133-.782.231-1.563.313-2.344-.092-.417-.272-.487-.5-.406zm-6.781 4.156c.151.019.235.204.25.531.016.365.206.661.437.72.183.045.167.238-.03.374-.116.08-.322.127-.688.125-.578-.003-.937-.153-1.25-.469l-.188-.187.281-.188c.142-.108.399-.332.563-.5.285-.29.473-.424.625-.406zm66.031-7.876a8.365 8.365 0 0 0-1.656.25c-1.04-.065-1.563 1.027-.563 1.563.602 1.534 1.54-.317 2.5-.188 1.438.28 1.56 1.832 1.781 3 .081 1.157.415 2.282.75 3.375.963 1.07-.72 1.74-1.437.906-.611-.664-1.92-1.48-2.656-.562-.904.382-.94 1.59-1.688 1.937-1.209.368-1.361-1.119-2-1.75-.587-.824-1.71-.896-2.625-1.187-.429-.869-.205-2.346-1.094-2.938-.745.304-2.113 1.702-.968 2.344 1.117.96-.488 1.401-1 2.063-.732.814-.849 1.936-.969 2.968-1.26.696-1.504-.787-1.656-1.718-.098-1.112-1.036-.786-1.688-.375-.952.385-1.428 1.29-2.094 2-.08.647.038 1.356.032 2.03.216.812 1.202.431 1.812.376.979-.41 1.38.627.594 1.219-.532.676-2.22.322-2.063 1.406.544.063 1.111.043 1.657 0 1.09-.298 2.261-1.068 2.375-2.281.143-1.059 1.667-.866 2.5-1.094 1.04-.3 2.294-.377 2.53.937.71.745 2.25 1.584 3.032.563.795-.485 1.176-1.338 1.125-2.25-.162-.785 1.269-.813 1.625-.375.521.858 2.151.605 2.938.125.836-.617 1.017-1.705 2.218-1.719 1.783-.534 3.635-.841 5.375-1.5 1.41-.307-.21-1.198-.562-1.719-1.074-.53-2.008 1.642-3.219.563-.936-.716-.872-2.077-1.219-3.125-.237-1.358-.177-2.923-1.156-4-.672-.715-1.586-.887-2.531-.844zm-6.813 9.469c.126-.003.268.06.5.187.439.242.751.643.75.969 0 .213-.054.227-.375.375-.197.091-.42.189-.5.188-.18-.002-.624-.357-.625-.5 0-.06-.058-.287-.125-.47-.117-.32-.099-.316.063-.53.103-.138.187-.216.313-.22zm6.532.344c.372-.025.593.091.75.375.181.329.058.58-.407.78-.203.089-.407.16-.437.157-.03-.003-.198-.102-.375-.219-.27-.177-.31-.264-.313-.468-.003-.316.35-.597.782-.625zm-8.938.093c.11-.017.209.04.344.156.18.155.237.28.281.594a2.23 2.23 0 0 1 0 .625c-.048.226-.053.216-.562.219-.64.006-.7-.064-.688-.656.008-.377.012-.478.219-.688.16-.162.297-.233.406-.25zm-5.5 1.438a.57.57 0 0 1 .438.437c.065.318.008.462-.25.594-.222.113-.734.15-.875.063a.613.613 0 0 1-.188-.188c-.068-.121-.055-.18.031-.25.06-.05.126-.12.125-.156 0-.037.068-.163.157-.281a.543.543 0 0 1 .562-.22zm9.25 1.187a.651.651 0 0 1 .438.156c.185.163.179.4-.031.563-.136.104-.872.095-1.125 0-.113-.042-.156-.099-.157-.219-.002-.14.038-.227.281-.344.205-.097.416-.155.594-.156zm-17.171 4.819c-.096-.063-.238-.117-.095-.222.173-.302.518-.407.825-.52a3.436 3.436 0 0 0 1.373-1.118c.05-.333.424-.513.422-.861.003-.475.032-.962-.084-1.426-.129-.426-.452-.752-.827-.974-.256-.202-.674-.258-.768-.614-.053-.343.253-.604.36-.91.223-.421.411-.863.651-1.275.26-.288.659-.015.793.263.19.277.357.576.45.897.303.332.571.721.68 1.162.148.31.383.602.369.966 0 .416.235.787.22 1.206.014.56.013 1.145-.191 1.674-.14.294-.421.47-.607.733-.319.295-.67.579-1.08.736-.289.092-.457.426-.819.345-.514.009-1.037.079-1.547-.004.032.054-.156-.092-.125-.058zm-6.85.45c-.243-.25-.295-.355-.298-.6-.003-.248.045-.346.282-.586.439-.443.653-.453 1.41-.07.722.365.967.399 1.032.14.062-.25.478-.48.874-.481a.82.82 0 0 1 .592.203c.251.196.263.227.27.68.004.463-.002.48-.29.736-.278.244-.323.259-.666.224-.437-.043-.7-.244-.77-.588-.052-.25-.14-.31-.206-.14-.021.055-.129.122-.239.15-.204.051-.549.268-.794.5-.093.087-.255.128-.519.131-.355.003-.405-.018-.678-.299zm-19.82-8.9c-.665.007-1.38.566-1.469 1.219.152.752.777 1.49.375 2.281.278 1.013-.761 1.397-1.469.813-.427-.972-.643-2.036-1.28-2.907-.805-.227-1.155 1.057-1.72 1.5.28.755 1.096 1.433 1.188 2.375.195.915-.361 1.93-1.156 2.406-.686.655-1.626.421-2.47.563-1.023.599.753.818 1.22.844 1.047.106 2.135-.032 2.906-.813.769-.367.71-1.697 1.625-1.844 1.588-.07 3.163.244 4.75.282.85.203 2.163-.101 2.75.53.002 1.108.94 1.791 1.844 2.22.498.138 1.024-.48 1.53-.594.966-.308.673-1.502 1.25-1.969 1.651-.09 3.317-.07 4.97-.093.314.007.407-.44.625-.626-.037-.638-.06-1.272-.157-1.906-.318-.806.052-1.844-.53-2.53-.83-.227-1.537.533-2.376.593-.926.412-1.706 1.268-1.75 2.312-.548.897-1.427-.16-1.125-.906-.034-.325.07-.704-.031-1-.507-.608-1.395-.41-2.094-.5-1.018.04-2.012-.18-3.031-.156-.893-.068-1.822.078-2.688-.156-1.031-.03-.89-1.039-1.062-1.75a1.018 1.018 0 0 0-.625-.188zm2 3.688c.343.006.667.051 1 .093.43.071.89-.148 1.313 0 .976.166 1.953.127 2.937.219.26-.004.446.185.625.344.002.683 0 1.379 0 2.062-.03.258.076.598-.156.781a.7.7 0 0 1-.25.125c-.27-.07-.558-.247-.688-.5-.041-.357.018-.704.031-1.062-.007-.093.04-.237 0-.313a1.248 1.248 0 0 0-.718-.25c-.85-.029-1.682-.091-2.531-.125-.707-.044-1.434.06-2.125-.125-.269-.097-.618-.064-.782-.343-.234-.273.104-.597.344-.72a2.28 2.28 0 0 1 1-.187zm11.281.25c.159-.003.21.05.281.343.046.188.1.417.125.5.037.118-.022.156-.187.219-.494.186-.986.168-1.156-.063-.078-.104.012-.434.156-.562.29-.259.61-.437.781-.438z'/%3e%3c/g%3e%3c/g%3e%3cpath stroke-width='1.15' d='M449.98 327.23c32.642-25.106 29.843-61.883 29.843-61.883a12.72 12.72 0 0 1-2.54.258c-6.848 0-23.179-3.917-26.989-8.892-4.081 4.503-20.77 8.892-27.574 8.892-.861 0-1.722-.086-2.54-.258 0 0-2.843 36.776 29.8 61.883z'/%3e%3cpath stroke-width='.916' d='M477.22 268.04a13.55 13.55 0 0 1-.848.026c-6.205 0-20.619-3.183-26.175-7.957-5.82 4.41-20.47 7.957-26.576 7.957a4.7 4.7 0 0 1-.85-.086c-.014 1.39.059 2.832.145 4.144.323 4.9 1.183 9.819 2.488 14.552 4.108 14.895 12.516 27.553 24.572 37.155 12.066-9.61 20.484-22.28 24.6-37.186 1.308-4.732 2.17-9.65 2.496-14.55.086-1.285.157-2.692.148-4.055z'/%3e%3cpath fill='%23c09300' stroke='none' d='M439.38 265.03c-5.872 1.845-12.229 3.031-15.75 3.031a4.7 4.7 0 0 1-.844-.093c-.014 1.39.07 2.845.156 4.156a72.77 72.77 0 0 0 2.47 14.53c2.764 10.026 7.506 19.033 13.968 26.782V265.03zm20.62-.09v49.25c6.794-7.921 11.733-17.206 14.594-27.562a72.952 72.952 0 0 0 2.469-14.531c.085-1.284.166-2.7.156-4.063-.28.018-.56.032-.844.032-3.73 0-10.42-1.17-16.375-3.125z'/%3e%3cg stroke-width='1.27'%3e%3cpath stroke-width='1.218' d='M462.31 253.09c.667.04-.902-3.568-.902-3.568 1.765 1.804 8.43 2.235 8.43 2.235-4-1.766-7.998-15.096-7.528-25.721.432-10.664-1.528-14.86-3.097-16.428-2-2-8.43-3.764-12.664-4-2.392-.117-2 1.804-2 1.804-4.43-1.137-8.86-1.568-10.86-.235-1.883 1.255-2.275 7.528-.902 6.43 3.332-2.666 6.234-.235 8.233 2.666 1.764 2.549 1.647 9.763-.902 18.192-2.666 8.861-9.959 17.722-9.959 17.722 3.96 0 9.528-3.528 9.528-3.528l-1.333 5.528c4.195-2 7.528-5.097 7.528-5.097l3.999 4.195c1.333-1.764 4-4.195 4-4.195s3.332 3.529 8.429 4z'/%3e%3cpath fill='none' d='M446.12 227.57s-2.235 16.428-6.43 21.094m9.96-21.524s-.863 16.623-3.764 21.956m6.894-21.286s0 18.192 1.098 21.289m2.862-20.389s.902 15.291 4.666 20.819'/%3e%3cpath fill='%23c09300' stroke-width='.354' d='M442.08 219.61c-.196-1.45-.549-2.588-1.059-3.333-2-2.901-4.9-5.332-8.233-2.666 0 0 1.137-3.529 3.568-3.646 1.882-.118 6.155 1.411 9.92 7.841 0 0-2.784-.627-3.45-.039-1.256 1.098-.746 1.843-.746 1.843z'/%3e%3cpath fill='%23c09300' stroke-width='.354' d='M432.44 209.26c.274-.902.706-1.725 1.255-2.078 2-1.333 6.43-.902 10.86.235 0 0-.392-1.921 2-1.803 4.234.235 10.664 2 12.663 3.999.47.51 1.02 1.255 1.49 2.391h-.078c-.98-1.372-3.764-1.293-4.431-1.215-1.059.118-1.725.078-3.137.431-.666.157-1.686.353-2.235.784-.43.353-.784 1.647-1.45 1.647-1.059 0-.98-.274-1.255-.588-.353-.431-.549-1.059-.902-1.02-1.097.197-2.862-.666-5.096-2.43-2.235-1.765-3.098-2.196-5.999-2-2.862.235-3.764 1.843-3.764 1.843l.079-.196z'/%3e%3ccircle cx='448.824' cy='210.672' r='1.176' stroke='none'/%3e%3c/g%3e%3c/g%3e%3c/svg%3e)
