Regeneration of Red Cell Cholinesterase Activity Following Pralidoxime (2-PAM) Infusion in First 24 h in Organophosphate Poisoned Patients

Oximes such as pralidoxime chloride reactivate acetylcholinesterase. However their role in management of organophosphate poisoning is controversial. The study was carried out to find effectiveness of pralidoxime chloride (2-PAM) in regenerating red cell acetyl cholinesterase in first 24 h following administration of it in dose recommended by WHO. Eight patients with OPP [chlorpyriphos (3), phorate (3), dichlorvos (1) and monocrotophos (1) who fulfilled the criteria for inclusion were investigated. In addition to decontamination and atropine, all these patients were administered 30 mg/kg body wt of 2-PAM as bolus dose followed by 7.5 mg/kg body wt/h with maximum dose being 500 mg/h as continuous infusion till first 24 h. Red cell AChE activity was estimated every 15 min for first 4 h, one hourly for next 4 h and then 2 hourly till 24 h and subsequently without 2-PAM every 12 h till 7 days or discharge or death which ever earlier. In all the patients maximum increase in activity was observed in first 4 h following which rise was very slow despite continued 2-PAM infusion and reaching a steady state in 20 h in all the cases. The increase in red cell AChE activity observed in diethyl group at 24 h of 2-PAM infusion was 154% vs. 81% in dimethyl group. At 7 days the increase in activity was 215% vs. 118% respectively. However on multiple repeated ANOVA, no statistically significant difference was observed between diethyl and dimethyl groups at admission and discharge (P > 0.05). Similarly no significant difference was observed in three groups when patients were categorized according to WHO classification of organophosphates (P > 0.05). The maximum increase in red cell AChE activity occurs in first 4 h of 2-PAM administration followed by a slow increase despite 2-PAM infusion till 24 h.     

Does LDL-C Estimation Using Anandaraja’s Formula Give a Better Agreement with Direct LDL-C Estimation than the Friedewald’s Formula?

Estimation of low density lipoprotein cholesterol (LDL-C) is crucial in management of coronary artery disease patients. Though a number of homogenous assays are available for estimation of LDL-C, use of calculated LDL-C by Friedewald’s formula (FF) is common in Indian laboratories for logistic reasons. Recently Anandaraja and colleagues have derived a new formula for calculating LDL-C. This formula needs to be evaluated before it is extensively applied in diagnosis. We measured LDL-C by homogenous method (D-LDL-C) in 515 fasting samples. Friedewald’s and Anandaraja’s formulas were used for calculation of LDL-C (F-LDL-C and A-LDL-C, respectively). The mean LDL-C levels were 123.3 ± 53.2, 112.4 ± 50.2 and 109.2 ± 49.8 mg/dl for D-LDL-C, F-LDL-C and A-LDL-C, respectively. There was a statistically significant difference between the results (P > 0.001) obtained by calculation formulas compared to the measured LDL-C. There was underestimation of LDL-C by 10.8 and 14 mg/dl by Friedewald’s and Anandaraja’s formulas respectively. The Pearson’s correlation between F-LDL-C and D-LDL-C was 0.931 and that between A-LDL-C and D-LDL-C was 0.930. Bland–Altman graphs showed a definite agreement between mean and differences of the calculation formulas and direct LDL-C with 95% of values lying with in ±2 SD limits. The mean percentage difference (calculated as {(Calculated LDL-C)-(D-LDL-C)}/D-LDL-C × 100) for F-LDL-C was maximum (−11.6%) at HDL-C ≥ 60 mg/dl and TG levels of 200–300 mg/dl (−10.4%) compared to D-LDL-C. A-LDL-C results gave highest mean percentage difference at total cholesterol concentrations <100 mg/dl (−37.3%) and HDL-C < 40 mg/dl (−17.1%), respectively. The results of our study showed that FF is better in agreement with D-LDL-C than Anandaraja’s formula for estimation of LDL-C by calculation though both lead to its underestimation.     

Nanotechnology: A Revolution in Cancer Diagnosis

Nanotechnology has brought revolution in cancer detection and treatment. It has capability to detect even a single cancerous cell in vivo and deliver the highly toxic drugs to the cancerous cells. Nanoshells, carbon nanotubes, quantum dots, supermagnetic nanoparticles, nano wires, nanodiamonds, dandrimers, and recently synthesized nanosponges are some of the materials used for cancer detection. Using specific cross linkers, such as specific antibodies against cancer cells individual cancer cells can be located. With the aid of a novel set of lipid-coated, targeted quantum dots a method for quantifying multiple specific biomarkers on the surfaces of individual cancer cells was also developed. This approach to quantitative biomarker detection stands to improve the histopathology methods used to diagnosis pancreatic and other cancers and enable the development of methods to spot cancer cells circulating in the blood stream. Certain nano materials can also deliver cancer drugs at the site so the drug toxicity can also be reduced.     

Silver Nano Particles Prevent Platelet Adhesion on Immobilized Fibrinogen

Vascular thrombotic disorders have emerged as a serious threat to our society. Platelet adhesion to fibrinogen, collagen and other platelet activators exposed over the atherosclerotic plaques can trigger platelet signaling events, activate platelets and lead to thrombotic events. Since anticoagulant and thrombolytic treatment strategies are usually associated with serious bleeding complications, preventing platelets adhesion may help to maintain platelets in an inactive state. In this study we tried to find out the effect of Silver nanoparticles, through their interaction with various platelet surface integrins on platelet adhesion on immobilized fibrinogen. Platelets, isolated from anti-coagulated human whole blood sample from healthy donors, were suspended in physiological buffer and each sample was divided into four tubes. In three of them 0.05, 0.5, and 5 μM concentrations of Silver nanoparticles were added, fourth tube served as control. Platelet adhesion on immobilized fibrinogen matrices and integrin mediated cell signaling events were studied in all the four samples. In the present study we show that nanosilver prevent platelet adhesion without conferring any lytic effect on them and effectively prevents integrin-mediated platelet responses in a concentration-dependent manner.     

Biochemical changes during exchange transfusion in hyperbilirubinemia in term newborn babies

Double volume (170 ml/kg body weight) exchange transfusion was done in 52 term infants in the first week of life for neonatal hyperbilirubinemia. The M:F ratio was 1.08:1 and 37 (71.1%) babies were of low birth weight. Causes of jaundice were hemolytic in 46.2% and non-hemolytic in 41.3% cases; in 13.5% babies no cause of jaundice could be found. After exchange transfusion a fall of 14.6% and 47.4% was observed in the hemoglobin and serum bilirubin levels respectively. There was significant (p=0.0414) rise in the mean mid exchange and post-exchange serum sodium levels as compared to pre-exchange values and it was found to be due to higher donor's serum sodium levels (p=0.007). There was no effect on the serum potassium levels during or after ET. In general serum calcium levels significantly increased at mid-exchange period (p=0.0029) but post-exchange levels were same as pre-exchange. Donor's serum calcium level had no effect on the infant's serum calcium level (p=0.993). There was no change in the serum phosphate and blood urea levels during and after exchange-transfusion. The plasma glucose was significantly raised during and after ET and plasma glucose of the donors had significant effect on the infant's plasma glucose levels (p=0.043). Similarly plasma osmolality also showed significant increase during and after ET which was due to the effect of donor's plasma osmolality (p=0.007).     

Role of oxidative stress in ethanol induced germ cell apoptosis — An experimental study in rats

The study was undertaken to evaluate the possible involvement of oxidative stress in the pathogenesis of ethanol induced testicular atrophy in rats. Adult male rats were orally administered ethanol at a dose of 1.6 g/kg body weight/day for four weeks. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and weighed. Apoptosis was studied by using the Feulgen reaction on 5 μ thin paraffin sections of testis. Testicular homogenate was prepared and centrifuged. The supernatant was used for the estimation of extent of lipid peroxidation and antioxidant defense status. There was significant reduction in body weight: and in testicular weight and diameter in ethanol treated rats. Extent of germ cell apoptosis was significantly high in ethanol treated rats. Ethanol treated rats showed significantly high tissue TBARS level and glutathione S-transferase activity; and low tissue ascorbic acid, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities. Chronic ethanol administration resulted in high oxidative stress in the testes either due to increased extent of lipid peroxidation or due to decreased antioxidant defenses, and thereby induces germ cell apoptosis leading to testicular atrophy.     

Oxygen derived free radicals in clinical context

Oxygen derived free radicals have been implicated in a number of clinical disorders including atherosclerosis (1), ischemic heart disease (IHD) (2), post ischemic reperfusion injury (3) and respiratory distress syndrome (4). These radical are generated by sequential reduction of molecular oxygen; the primary product being superoxide anion (O₂ ^.−) which is subsequently reduced to hydrogen peroxide (H₂O₂), hydroxy1 radical (OH^.) and singlet oxygen (¹O₂). However the evidence for ODFR induced cell damage in various clinical disorders is still debated and rests largely on free radical scavenging studies, through electron paramagnetic resonance spectroscopic (EPRS) studies have provided direct evidence for ODFR generation following coronary artery ligation (5). By definition, a free radical is an atom, ion or molecule with one or more unpaired electrons (the presence of unpaired electron in a free radical being represented by a superscribed bold dot-R^.) and may be formed as a result of homolytic fission of a covalent bond or by electron transfer reactions, and may have cationic (NH₃ ⁺), anionic (O₂ ^.−) or neutral (NO) characteristics. The most important in vivo source for these radical species have been found to be univalent biochemical redox reactions involving oxygen. (a) A:B→A^.+B^. (b) A:+B→A^.+B^.