Role of ALAD and VDR genotypes on the association of low blood lead level with serum uric acid and blood pressure in automobile paint workers of Karachi, Pakistan.

Lead is an environmental pollutant having nephrotoxic effects even at low level. Its continuous exposure is associated with increased serum uric acid level that resulting in renal insufficiency. This research was conducted to see the effects of delta-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genotypes on biochemical parameters and blood pressure (BP) of automobile workers having low blood lead level (BLL) with continuous lead exposure. Automobile paints workers with ALAD 1-2 genotype showed the positive association of BLL with diastolic BP (p<0.05) whereas, a genotypic combination of ALAD 1-2/VDR BB showed the negative association of serum uric acid with BLL (p<0.05). Similarly negative effects of VDR BB genotype (p<0.01) and ALAD 1-2 genotype (p<0.05) were observed in the association of serum uric acid with BLL at the mean age ≥30 years. This suggests that automobile paint workers having ALAD 1-2 genotypes are at the risk of increased diastolic BP. The research also foretells that combination of ALAD 1-2/VDR BB may play a significant role against lead induced nephrotoxicity at low BLL with continuous lead exposure.

Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice.

Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

Effect of Grewia asiatica fruit on glycemic index and phagocytosis tested in healthy human subjects.

The Grewia asiatica (commonly known as Phalsa or Fasla) is a shrub or small tree found in southern Asia. It produces purple to black color fruit when ripe. In folk medicine the edible Grewia asiatica fruit is used in a number of pathological conditions. The current study described the effects of Grewia asiatica fruit on glycemic index (GI) and phagocytosis in healthy non-diabetic human subjects. The results showed that Grewia asiatica fruit has low GI value of 5.34 with modest hypoglycemic activity. Luminol-enhanced chemiluminescence assay was carried out to determine the production of reactive oxygen species (ROS) in the oxidative burst activity of whole blood. ROS production was found to be significantly affected, having the 78.3, 58.6 and 30.8% when the subjects were fed with D-glucose, mixture of D-glucose and Grewia asiatica fruit and Grewia asiatica fruit alone respectively as compared to the control. The aqueous, methanolic and butanolic extracts of Grewia asiatica fruits were found to produce a stimulatory effect on ROS production however; the chloroform, hexane and ethanol-acetate extracted exerted significant inhibitory effect. These results demonstrated that Grewia asiatica fruit has desirable effects on blood glucose metabolism manifested as low glycemic response and modulation of ROS production.

Evaluation of teratogenic effects of risperidone following simultaneous administration with antihypertensive and antiemetic drugs.

Multiple drug administration is an important aspect of clinical practice particularly in specific physiological situation such as in neonates, elderly or pregnancy, since in all such situations, possibility of unwanted effects increases due to altered body physiology. In present study, the teratogenic effects of multiple drug administration risperidone, meclizine/pyridoxine and hydralazine have been compared with the teratogenic effects of individual drugs in pregnant mice. Moreover the role of folic acid and α-tocopherol if any had also been investigated in reducing the teratogenic effects of these drugs in combinations.