Epidemiological Characteristics of Poliomyelitis During the 21st Century (2000-2013)

Poliovirus is the pathogenic agent of paralytic poliomyelitis that belongs to the picornaviridae family. Poliomyelitis has an extended history dating over to the Egyptian eighteenth dynasty. It was recognized as distinct disease in the late nineteenth century when the world was ravaged by large number of outbreaks and epidemics in many countries. Paralytic Polio, the rarest but the most severe form of the disease, is characterized by acute flaccid paralysis of any or rarely both of the limbs. Increasing epidemics during the late 19th and 20th centuries lead to the initiation of a worldwide global effort for polio eradication in 1988, super headed by WHO and various other organizations. The launch of Global Polio Eradication Initiative together with the introduction of two polio vaccines resulted in 99% reduction of wild poliovirus cases worldwide while the total number of polio-endemic countries dropped from 24 countries in the year 2000 to only three countries in 2012; Afghanistan, Nigeria and Pakistan. This review will focus on the general biology of poliovirus, some historic and geographic epidemiological aspects of poliomyelitis eradication during the year 2000-2012 and also on the major failing factors associated with the efficiency of the vaccines to eradicate polio in Pakistan

Aqueous Fraction of <i>Beta vulgaris</i> Ameliorates Hyperglycemia in Diabetic Mice due to Enhanced Glucose Stimulated Insulin Secretion, Mediated by Acetylcholine and GLP-1, and Elevated Glucose Uptake via Increased Membrane Bound GLUT4 Transporters

<div><p>Background</p><p>The study was designed to investigate the probable mechanisms of anti-hyperglycemic activity of <i>B. Vulgaris</i>.</p><p>Methodology/Principal Findings</p><p>Aqueous fraction of <i>B. Vulgaris</i> extract was the only active fraction (50mg/kg). Plasma insulin level was found to be the highest at 30 mins after <i>B. Vulgaris</i> administration at a dose of 200mg/kg. <i>B. Vulgaris</i> treated mice were also assayed for plasma Acetylcholine, Glucagon Like Peptide-1 (GLP-1), Gastric Inhibitory Peptide (GIP), Vasoactive Intestinal Peptide, Pituitary Adenylate Cyclase-Activating Peptide (PACAP), Insulin Like Growth Factor-1 (IGF-1), Pancreatic Polypeptides (PP), and Somatostatin, along with the corresponding insulin levels. Plasma Acetylcholine and GLP-1 significantly increased in <i>B. Vulgaris</i> treated animals and were further studied. Pharmacological enhancers, inhibitors, and antagonists of Acetylcholine and GLP-1 were also administered to the test animals, and corresponding insulin levels were measured. These studies confirmed the role of acetylcholine and GLP-1 in enhanced insulin secretion (p<0.05). Principal signaling molecules were quantified in isolated mice islets for the respective pathways to elucidate their activities. Elevated concentrations of Acetylcholine and GLP-1 in <i>B. Vulgaris</i> treated mice were found to be sufficient to activate the respective pathways for insulin secretion (p<0.05). The amount of membrane bound GLUT1 and GLUT4 transporters were quantified and the subsequent glucose uptake and glycogen synthesis were assayed. We showed that levels of membrane bound GLUT4 transporters, glucose-6-phosphate in skeletal myocytes, activity of glycogen synthase, and level of glycogen deposited in the skeletal muscles all increased (p<0.05).</p><p>Conclusion</p><p>Findings of the present study clearly prove the role of Acetylcholine and GLP-1 in the Insulin secreting activity of <i>B. Vulgaris</i>. Increased glucose uptake in the skeletal muscles and subsequent glycogen synthesis may also play a part in the anti-hyperglycemic activity of <i>B. Vulgaris</i>.</p></div

Effects of aqueous fraction of <i>Beta vulgaris</i> (BV) on A) cAMP content, B) Protein Kinase A (PKA) activity, and C) Insulin secretion from isolated mouse islets after a 30mins incubation period.

<p>Values are means and standard deviation (SD) represented by vertical bars (n = 4). Groups of 25–30 islets were isolated from db/db diabetic mice after collagenase digestion. The mice were fed with <i>B. Vulgaris</i> (200 mg/kg) for 8weeks before the isolation procedure. Isolated islets were exposed to 5.6mM glucose for 60minsto adapt to a baseline glucose concentration. Then they were exposed to 16.7mM glucose alone (untreated group) or to <i>B. Vulgaris</i> (50 μg/ml) or to <i>B. Vulgaris</i> (50 μg/ml)+Ext9 (Extendin 9–39) (2μmol/l) for 30mins. At the same time, the groups were also exposed to GLP-1 14.7pmol/l (untreated group), 21.4 pmol/l (<i>B. Vulgaris</i> treated group), and 21.5pmol/l (<i>B. Vulgaris</i>+Extending 9–39 treated group) (concentrations of GLP-1 found during in vivo test in response to different treatments at 30mins). After the incubation period, samples were collected or islets were sonicated, where required, and equivalent amount of islet protein was analyzed. Values marked with an asterisk (*) or two (**) were significantly higher from the control group value with p<0.05 or p<0.01 respectively (Derived from One-way ANOVA followed by post hoc Dunnett’s test).</p

Effects of aqueous fraction of <i>Beta vulgaris</i> (BV) on A) blood glucose level and B) plasma insulin level during a glucose tolerance test in diabetic db/db mice.

<p>Values are means and standard deviations (SD) represented by vertical bars (n = 10). Fasted mice were orally given aqueous fraction of <i>B. Vulgaris</i> (50 mg/kg, 100 mg/kg, and 200 mg/kg body weight) or vehicle for control group(water; 10 ml/kg)with glucose (2.5 g/kg body weight). Mean values marked with an asterisk (*) or two (**) were significantly different from those of respective control group at p<0.05 and p<0.01 respectively. (Derived from repeated-measures ANOVA and adjusted using Bonferroni correction).</p

Effects of aqueous fraction of <i>Beta vulgaris</i> (BV) on A) GLUT 1 level & B) GLUT 4 level in skeletal smooth muscle membrane, C) Hexokinase II activity, D) Glucose-6-Phosphate (g-6-P) content, E) Glycogen synthase activity, and F) Glycogen content in skeletal smooth muscle in different treatment groups of db/db diabetic mice at 1h after glucose load is given.

<p>Values are means and standard deviation (SD) represented by vertical bars (n = 8). Fasted mice were orally given aqueous fraction of <i>B. Vulgaris</i> (200 mg/kg) or vehicle (water; 10 ml/kg) along with a glucose load (2.5 g/kg body weight) 1h before the smooth muscle membrane and smooth muscle was collected and processed as described in the material and method section for analysis. Mean values marked with an asterisk (*) were significantly higher from the associated control group value with p<0.05 (Derived from Student’s t-test).</p

Effects of aqueous fraction of <i>Beta vulgaris</i> (BV) on A) Phospholipase C activity, B) Diacylglycerol (DAG) level, C) Protein Kinase C (PKC) activity, and D) Insulin secretion from isolated mouse islets after 30mins of incubation.

<p>Values are means and standard deviation (SD) represented by vertical bars (n = 4). Groups of 25–30 islets were isolated from db/db diabetic mice after collagenase digestion. The mice were fed with <i>B. Vulgaris</i> (200 mg/kg) for 8weeks before the isolation procedure. Isolated islets were exposed to 5.6mM for 60mins glucose to adapt to a baseline glucose concentration. Then they were exposed to 16.7mM glucose alone (untreated group), with <i>B. Vulgaris</i> (50 μg/ml) or with <i>B. Vulgaris</i> (50 μg/ml)+Atropine (1mmol/l) for 30mins. At the same time, the groups were also exposed to Acetylcholine 123 pg/ml (untreated group), 198 pg/ml (<i>B. Vulgaris</i> treated group), and 189 pg/ml (<i>B. Vulgaris</i>+Atropine treated group) (concentration of Acetylcholine found during in-vivo test in response to different treatments at 30mins). After the incubation period, samples were collected or islets were sonicated where required and equivalent amount of islet protein was analyzed. Values marked with an asterisk (*) were significantly higher from the control group value with p<0.05 (Derived from One-way ANOVA followed by post hoc Dunnett’s test). In case of PLC activity, we define 1 unit of enzyme activity as the amount that transfers 1 μmol of PI/min.</p

Effects of aqueous fraction of <i>Beta vulgaris</i> (BV) on A) plasma Acetylcholine level and B) associated plasma Insulin level in different treatment groups of db/db diabetic mice at 30mins after glucose load is given.

<p>Values are means and standard deviation (SD) represented by vertical bars (n = 9). Fasted mice were orally given aqueous fraction of <i>B. Vulgaris</i> (200 mg/kg) alone or with different drugs, injected intravenously 30mins before <i>B. Vulgaris</i> administration, with a glucose load (2.5 g/kg body weight). Untreated group received only vehicle (water; 10 ml/kg). Atropine: A muscarinic receptor antagonist; dose 0.1 mg/kg. HCM-3: Hemicholinium-3, a choline uptake blocker; dose 0.1 mg/kg. VML: Vesamical, an inhibitor of vesicular acetylcholine transport; 3.5 mg/kg. PTM: Physostigmine, a reversible cholinesterase inhibitor; dose 0.5 mg/kg. Mean values marked with an asterisk (*) or two (**) or three (***) were significantly higher from the control group value with p<0.05 or p<0.01 or p<0.001 respectively (Derived from One-way ANOVA followed by post hoc Dunnett’s test).</p

Effects of aqueous fraction of <i>Beta vulgaris</i> (BV) on A) plasma GLP 1 level and B) associated plasma Insulin level in different treatment groups of db/db diabetic mice at 30mins after glucose load is given.

<p>Values are means and standard deviation (SD) represented by vertical bars (n = 10). Fasted mice were orally given aqueous fraction of <i>B. Vulgaris</i> (200 mg/kg) alone or with different drugs along with a glucose load (2.5 g/kg body weight). Untreated group received only vehicle (water; 10 ml/kg).</p