EFFECT OF SHORT COURSE CHEMOTHERAPY ON SALIVARY PARACETAMOL ELIMINATION

1. Salivary elimination of paracetamol was studied in six male pulmonary tuberculosis patients on short course chemotherapy. 2. Peak paracetamol concentration showed a steady decrease at the end of first week and continued until the end of the study. 3. The elimination half-life of paracetamol decreased 5 weeks after the therapy with a corresponding increase in the clearance rate. 4. Adjustment of dosage of drugs that are metabolized by the microsomal enzymes may be required in patients on anti-tubercular drug regimen in which rifampicin is included.     

Increasing mean arterial blood pressure in sepsis: effects on fluid balance,vasopressor load and renal function

Introduction

The objective of this study was to evaluate the effects of two different mean arterial blood pressure (MAP) targets on needs for resuscitation, organ dysfunction, mitochondrial respiration and inflammatory response in a long-term model of fecal peritonitis.

Methods

Twenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8/group) to a septic control group (septic-CG) without resuscitation until death or one of two groups with resuscitation performed after 12 hours of untreated sepsis for 48 hours, targeting MAP 50-60 mmHg (low-MAP) or 75-85 mmHg (high-MAP).

Results

MAP at the end of resuscitation was 56 ± 13 mmHg (mean ± SD) and 76 ± 17 mmHg respectively, for low-MAP and high-MAP groups. One animal each in high- and low-MAP groups, and all animals in septic-CG died (median survival time: 21.8 hours, inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the high-MAP group (0.38 (0.21-0.56) mcg/kg/min), and to three animals of the low-MAP group (0.00 (0.00-0.25) mcg/kg/min; P = 0.009). The high-MAP group had a more positive fluid balance (3.3 ± 1.0 mL/kg/h vs. 2.3 ± 0.7 mL/kg/h; P = 0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between low- and high-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for low- and high-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (P = 0.026). In septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357 ± 149 pmol/s/mg to 1822 ± 385 pmol/s/mg, (P = 0.020). In high- and low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (P = 0.003).

Conclusions

The MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of different MAP targets need to be evaluated in further studies.     

Hepatoprotective and antioxidant activity of aqueous extract of Hybanthus enneaspermus against CCl4-induced liver injury in rats

The hepatoprotective, curative and anti-oxidant properties of aqueous extract of Hybanthus enneaspermus (Violaceae) used against CCl4-induced liver damage in rats were investigated in the present study. Liver damage was induced by CCl4 (1 ml/kg i.p.), and silymarin was used as a standard drug to compare hepatoprotective, curative and antioxidant effects of the extract. Rats were treated with aqueous extract of H. enneaspermus at a dose of either 200 or 400 mg/kg after division into pre-treatment (once daily for 14 days before CCl4 intoxication) and post-treatment (2, 6, 24 and 48 h after CCl4 intoxication) groups. Pre-treatment and post-treatment with aqueous extract of H. enneaspermus showed significant hepatoprotection by reducing the aspartate transaminase, alanine transaminase, and alkaline phosphatase enzymatic activities and total bilirubin levels which had been raised by CCl4 administration. Pre- and post-treatment with aqueous extract significantly decreased hepatic lipid peroxidation as well as producing a corresponding increase in tissue total thiols. Post-treatment with aqueous extract improved ceruloplasmin levels. The histopathological examination of rat liver sections treated with aqueous extract confirms the serum biochemical observations. The present study results demonstrate the protective, curative and anti-oxidant effects of H. enneaspermus aqueous extract used against CCl4-induced hepatotoxicity in rats, and suggest a potential therapeutic use of H. enneaspermus as an alternative for patients with acute liver diseases.