Pratima Srivastava

Synergistic effect of intrathecal fentanyl and bupivacaine in spinal anesthesia for cesarean section

BackgroundPotentiating the effect of intrathecal local anesthetics by addition of intrathecal opiods for intra-abdominal surgeries is known. In this study by addition of fentanyl we tried to minimize the dose of bupivacaine, thereby reducing the side effects caused by higher doses of intrathecal bupivacaine in cesarean section.MethodsStudy was performed on 120 cesarean section parturients divided into six groups, identified as B8, B10 and B 12.5 8.10 and 12.5 mg of bupivacaine mg and FB8, FB10 and FB 12.5 received a combination of 12.5 μg intrathecal fentanyl respectively. The parameters taken into consideration were visceral pain, hemodynamic stability, intraoperative sedation, intraoperative and postoperative shivering, and postoperative pain.ResultsOnset of sensory block to T6 occurred faster with increasing bupivacaine doses in bupivacaine only groups and bupivacaine -fentanyl combination groups. Alone lower concentrations of bupivacaine could not complete removed the visceral pain. Blood pressure declined with the increasing concentration of Bupivacaine and Fentanyl. Incidence of nausea and shivering reduces significantly whereas, the postoperative pain relief and hemodynamics increased by adding fentanyl. Pruritis, maternal respiratory depression and changes in Apgar score of babies do not occur with fentanyl.ConclusionSpinal anesthesia among the neuraxial blocks in obstetric patients needs strict dose calculations because minimal dose changes, complications and side effects arise, providing impetus for this study. Here the synergistic, potentiating effect of fentanyl (an opiod) on bupivacaine (a local anesthetic) in spinal anesthesia for cesarian section is presented, fentanyl is able to reduce the dose of bupivacaine and therefore its harmful effects.

Heme oxygenase and related indices in chloroquine-resistant and -sensitive strains of Plasmodium berghei

Chloroquine-resistant (CQR) and -sensitive (CQS) Plasmodium berghei K173 strains possessed significant activities of heme oxygenase, biliverdin reductase and heme polymerase. Heme oxygenase and biliverdin reducatase activities of CQR were significantly higher (7-10 fold) as compared to that of CQS P. berghei, whereas heme polymerase showed a reverse trend (two-fold decrease). However, a 10-fold increase in heme, three-fold increase in ferriprotoporphyrin IX and a two-fold increase in hemozoin levels were noted in CQS as compared to CQR strains of P. berghei. This study suggests the importance of heme oxygenase and related components in the biochemical regulation of malaria parasites and in understanding the mechanism of the acquisition of chloroquine resistance.

Heme metabolism in promastigotes of Leishmania donovani

Promastigotes of Leishmania donovani (Dd-8 strain) showed presence of important key enzymes of heme synthesizing (d-aminolevulinic acid synthase and ferrochelatase) and degrading (heme oxygenase and biliverdin reductase) systems, classical leishmanicidal drugs viz allopurinol, amphotericin B, pentamidine and CDRI compound 93/202 inhibited the heme oxygenase activity of the parasite, whereas, δ-aminolevulinic acid synthase activity practically remained unaffected. The Km, Vmax ad pH values of heme oxygenase of promastigotes were found to be 1666 μM hemin, 625 nmol of bilirubin formed h-1 mg protein-1 and 7.5 respectively. The findings suggest the presence and importance of heme metabolism in the de novo synthesis of different hemoproteins of the Leishmania parasite as well as the detoxification and its defence against biological insults.

Status of oxidative stress and antioxidant defences during Plasmodivm knowlesi infection and chloroquine treatment in Macaca mulatta

Plasmodium knowlesi (a simian malarial parasite) infection resulted in elevation of hepatic oxidative stress in monkeys. Further, the antioxidant defence system of the host was also noticeably affected. The infected monkeys showed a marked increase in the levels of superoxide (O2-), lipid peroxidation (LPO), glutathione (GSH) and xanthine oxidase (XO), and decreased levels of superoxide dismutase (SOD) and catalase. Oral administration of chloroquine (20 mg kg body wt-1 for 3 days) to infected monkeys caused recovery trends in oxidative stress and antioxidant defences to almost normal a week after cessation of drug treatment.

Potential inhibitors of plasmodial heme oxygenase; an innovative approach for combating chloroquine resistant malaria.

Syntheses of imidazo-pyridines and substituted prolines and their effect on heme oxygenase activity of Plasmodium yoelii and corresponding infected host have been studied. Six compounds in vitro and one in vivo showed selective inhibition of parasite enzyme which may be further exploited in the development of resistant reversal agents.

Effect of Plasmodium berghei infection and chloroquine on the hepatic drug metabolizing system of mice

The hepatic microsomal mixed-function oxidase (MFO) system was markedly impaired during Plasmodium berghei infection in mice. Cytochrome P-450 and other mono-oxygenases, viz. aniline hydroxylase, aminopyrine-N-demethylase and benzo(a)pyrene hydroxylase, were significantly decreased while microsomal heme showed a four-fold increase at peak parasitemia (greater than 50%). Oral treatment with chloroquine (16 mg kg-1 body wt for 4 days) of P. berghei-infected mice cleared the parasitemia within 72 h and almost normalized the altered levels of MFO indices, a week after cessation of treatment. The findings were further supported by the isoenzymic profile and drug-binding properties of terminal mono-oxygenase, cytochrome P-450.

Mitochondrial heme oxygenase of Mastomys coucha

While studying the fate of heme generated during malaria infection, it was observed that mitochondrial preparations were highly enriched with heme compared to other subcellular particles. With this background, the present study aimed to determine the status of mitochondrial heme oxygenase and compare it with the microsomal enzyme. Mitochondrial and microsomal preparations were obtained from liver, spleen, kidney and brain of normal, inducer (cobalt chloride and hemin)-treated and Plasmodium berghei-infected Mastomys coucha. Heme oxygenase activity was determined by monitoring the formation of bilirubin. Biliverdin reductase activity was assayed by following the decrease in biliverdin content. Heme levels were measured by pyridine haemochromogen formation. Mitochondria from different tissues showed significant activity of heme oxygenase only after inducer (CoCl2 and hemin) treatment. In contrast, cerebral mitochondria did not show any enzyme activity. Hepatic, splenic and renal mitochondria of P. berghei-infected M. coucha showed noticeable heme oxygenase and biliverdin reductase activity. The response of hepatic mitochondrial heme oxygenase towards Triton X-100, trypsin, hydrogen peroxide, temperature, freezing and thawing and hemin was distinguishable from microsomal heme oxygenase. It is concluded that the mitochondria of different tissues from Mastomys display stress (biological and chemical)-induced activity of heme oxygenase. In addition, distinct differences between microsomal and mitochondrial heme oxygenase were observed.

Effect of chloroquine on hepatic heme-oxygenase during Plasmodium berghei infection in mice

Hepatic heme-oxygenase and heme levels were monitored during Plasmodium berghei infection and chloroquine treatment in Swiss albino mice. A progressive increase in heme-oxygenase and heme levels was noticed with the rise in parasitemia. Further, chloroquine treatment did not result in any change towards normal heme-oxygenase and heme content, when they were assayed a week after cessation of drug treatment. Chloroquine treatment of non-parasitized and parasitized mice resulted in significant loss of the enzyme activity after about 6 weeks.

In situ absorption and protein binding characteristics of CDRI-85/92, an antiulcer pharmacophore.

CDRI-85/92, a new antiulcer drug, acts as a proton pump inhibitor arresting the secretion of acid in the stomach. The absorption kinetics of CDRI-85/92 was evaluated in situ using rat intestinal recirculation perfusion method. The experiment was conducted at pH 2.6 and 7.4 representing the acidic and the mild alkaline environment, which the drug experiences through the GIT during oral treatment. The rate of absorption was the same (0.12h(-1)) at pH 2.6 and 7.4, thus suggesting equal absorption profile of the CDRI-85/92 throughout the GIT irrespective of the pH. Equal rates of absorption can also be correlated with the presence of acidic and basic groups in the structure of CDRI-85/92. Protein binding studies of CDRI-85/92 using ultrafiltration were conducted in vitro and in vivo. Protein binding was found to be in the range of 31.49-32.91% both in in vitro and in vivo (employing 5-min post dose samples of rat serum after 20 mgkg(-1) i.v. treatment of CDRI-85/92). The binding was found to be linear in the concentration range of 156.25-2000 ngml(-1) (r(2)>0.99).

A Randomised Double-Blinded Dose Response Study of the Fentanyl with Hyperbaric Ropivacaine in Cesarean Section

Background: Much research work has been done to know the minimum required concentration of local anaesthetic agents, employing various adjuvants for cesarean section. The present study states that Fentanyl addition to heavy Ropivacaine reduced the dose of later, thereby its side effects related to higher doses in cesarean sections. Patients: Three groups of thirty parturient each were made randomly. Group I received 15 mg 0.6% Ropivacaine; Group II received 12 mg 0.6% Ropivacaine and 12.5 μg Fentanyl and Group III received 10 mg 0.6% Ropivacaine and 25 μg Fentanyl. Sensory and motor block properties, hemodynamics, intraoperative visceral pain, sedation, shivering, nausea and vomiting, postoperative analgesia; foetal outcomes and side effects were evaluated. ANOVA, chi-square and Mann-Whitney-U tests were used where appropriate (p<0.05). Results: Intrathecal hyperbaric Ropivacaine and its combination with Fentanyl provided effective sensory and motor block (1.73-2.1 min, p value<0.001), S2 dermatome regression time was longer in Ropivacaine- Fentanyl combination as compared to Ropivacaine alone. Umbilical venous pH and APGAR score was similar (9-9.4) in all groups. Postoperative analgesic effect (monitored as a secondary end-point) was prolonged by addition of Fentanyl; here intraoperative ephedrine requirement was significantly increased in group I (30 mg) as compared to group II (8 mg) and III (6 mg). Conclusions: S2 dermatome regression time taken as the primary end point was longer in Ropivacaine- Fentanyl combination as compared to Ropivacaine alone. Addition of 12.5 and 25 μg Fentanyl significantly reduced the dose of heavy Ropivacaine resulting in longer, complete and effective analgesia with hemodynamic stability and less side-effects. It is concluded that intrathecal hyperbaric Ropivacaine provides efficient and safe anaesthesia for cesarean section delivery and that this effect is further enhanced by the addition of Fentanyl. Hence the best effective and safe combination, as per this study is 12 mg of Ropivacaine with 12.5 μg Fentanyl (Group II).