Subacute toxicity study of the ethanolic extract of Mesua ferrea (L.) flowers in rats.

Mesua ferrea Linn. is used traditionally in India and South East Asian countries as an antiseptic, antidote and a brain tonic. Recent pharmacological studies on the plant have highlighted M. ferrea to be a rich source of secondary metabolites, with proven therapeutic applications. Since the toxicity of a plant following repeated exposure is of higher clinical significance, the present investigation was conducted to establish the subacute toxicity profile of the ethanolic extract of Mesua ferrea flowers (MFE). The study was conducted in accordance with the OECD Guideline 407, wherein MFE was administered orally to groups of male and female rats (n = 5/group/sex) at the doses of 100, 500 and 1000 mg/kg, over a period of 28 days. Repeated administration of MFE had no adverse effect on the growth rate and hematological parameters of the animals. There were no changes in the biochemical parameters, except for a slight decrease in the CHOL (total cholesterol) levels, and an increase in the levels of AST (aspartate aminotransferase) and ALT (alanine aminotransferase), at the highest dose. The latter corroborated with the histopathological findings exhibiting mild lymphocytic infiltration and hepatocyte degeneration observed in the liver tissues of both sexes. According to the study, the no-observed-adverse-effect level (NOAEL) of M. ferrea in the 28-day repeated dose toxicity study in rats was 500 mg/kg. Though the overall effects of the extract at the highest dose did not translate into any serious complications, its effect on hepatic function needs to be established over a longer period of study.

Septic pulmonary embolism: Is it an underestimated diagnosis?

Background: Non-thrombotic pulmonary embolism, an uncommon entity, is defined as the embolization of tissues, microorganisms, air, or foreign material. One subset in this non-thrombotic category is septic pulmonary embolism (SPE) that refers to embolism of microorganisms with or without a thrombotic mantle into the pulmonary vasculature. This condition is often recognized on the basis of imaging with a clinical correlation. Unfortunately, data regarding the pathological features are meager. This has prompted to review such cases at autopsy. Aims: To study the pathological features of SPE at autopsy. Materials and Methods: Ten-year (2012 to 2021) autopsy records of the hospital were retrospectively reviewed. The diagnosis was based on the identification of acute necrotizing pulmonary arteritis with peri-bronchoarterial consolidation. These cases were analyzed with reference to the demographics, clinical characteristics, and pulmonary/extrapulmonary findings at autopsy. Statistical Analysis: Nil. Results: According to the inclusion criterion, 19 cases demonstrated the presence of SPE. There were 11 men and 8 women with a mean age of 32.1 years. The major source of infection included infection arising from skin and musculo-skeletal system (11 patients, 59.7%). The common clinical presentation included fever, dyspnea, chest pain, hemoptysis, and altered sensorium. The cause of death was mainly due to septicemia and/or confluent lung consolidations. A large number of bacterial colonies were seen in all; Candida species were also identified in two cases. Other lung findings included diffuse alveolar damage, fresh arterial thrombosis, infarction, arterial pseudo-aneurysms, abscess formation, and pyogenic pleuritis. Conclusion: Presence of an extrapulmonary infection with persistent fever, bacteremia, and pulmonary complaints should raise suspicion for this entity, particularly in resource-poor settings, to prevent grave pulmonary complications.

Impact of protein deficient diet on the pharmacokinetics of glibenclamide in a model of malnutrition in rats.

Purpose: The present investigation deals with the impact of protein energy malnourished condition on the pharmacokinetic profile of glibenclamide. Protein energy malnourished condition leads to malnutrition related diabetes mellitus (MRDM), Fibrocalculus pancreatic diabetes mellitus (FCPD) or Lean body mass diabetes mellitus (LBMDM). Method: In the present study, malnutrition was developed in female wistar rats using a modified protein deficient diet (0.5%). The experiment was performed on 12 animals, each group containing 6 female wistar rats. The control group animals were fed with standard pellet diet (AIN 93 G diet) while group 2 received the low protein diet (0.5%) for 75 days. Glibenclamide (Gli) suspension (30 mg/kg) was administered orally to these rats on 75 days and kinetic parameters were evaluated by HPLC analysis.The pharmacokinetic interpretation done by pksolver software version 2.0, statistical comparison done by applying student T test. Results: The results of body weight and hematological parameters indicated a significant decreased in the body weight in protein deficit rats to 124.1 ± 6.2 g compared to 235.5 ± 8.4 g (p < 0.01) control rats; whereas a decrease in the hemoglobin to 5.8 ± 0.6 g/dL, total blood protein level to 6.9 ± 0.6 g/dL and blood albumin levels to 2.7 ± 0.4 g/dL in protein deficit rats compared to 15 ± 0.7 g/dL(p < 0.05), 8.1 ± 0.4 g/dL(p < 0.05), and 4.5 ± 0.2 g/dL(p < 0.05), respectively in control rats. All these findings reflect the malnourished condition and weight loss due to a protein deficit diet in experimental animals. There was an increase in the fasting blood glucose levels up to 150 ± 17.4 mg/dL in the protein deficit diet group as compared to 98.7 ± 14.1 mg/dL(p < 0.05) in control rats reflect the prediabetes state in malnourished animals. The results of the pharmacokinetic study reflect a significant lowering of half-life (T½) of glibenclamide to 96.8 ± 0.8 min. in malnourished rats compared to 166.7 ± 0.74 min. (p < 0.001) in control rats. The maximum concentration (Cmax) of glibenclamide in the malnourished rats was significantly higher 20.74 ± 0.65 µg/mL and also took double time i.e. about 180 min. to reach maximum concentration (Tmax) compared to the control rats values 7.9 ± 0.84 µg/mL (p < 0.001) and 90.0 ± 0.24 min. (p < 0.001) respectively. The area under the plasma concentration-time curve [AUC(0-∞)] in malnourished rats increased 4439.1 ± 40.6 µg/ml*min as compared to 1235.9 ± 55.8 µg/ml*min (p < 0.001) in control rats. There was a lowering in the total body clearance (CL) to 0.4 ± 0.02 L/hr and volume of distribution (Vd) to 1.75 ± 0.07 L of glibenclamide in the protein deficit group compared to 1.4 ± 0.3 L/hr (p < 0.001) and 3.14 ± 0.8 L (p < 0.01), respectively in the control rats. Conclusion: From this study it concludes that there is an increase in the T½, Cmax, Tmax and AUC(0-∞) of glibenclamide in malnourished rats while the total body clearance and volume of distribution is lowered. Therefore this study proposes to conduct an adequate pharmacokinetic study in malnourished patients to decide whether the standard glibenclamide dose should be adapted according to the nutritional status of the individual.

Peri-adventitial smooth muscle - inheritance of the iliac arterial system?

The histo-morphology of the arterial walls is typically made of 3 distinct layers or tunics designated as intima, media and adventitia. Based on the composition of the media, the arteries are classified into elastic and muscular types. The common iliac artery is an elastic artery, whereas its branches, the external and internal iliac arteries are muscular arteries. In this study, the presence of smooth muscle bundles outside the adventitia was noted in 93 samples taken from the iliac arterial system and the reasons for their presence have been hypothesized.