Dysregulated Genes and Signaling Pathways in the Formation and Rupture of Intracranial Aneurysm.

Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture.

Expressional Study of Permeability Glycoprotein and Multidrug Resistance Protein 1 in Drug-resistant Mesial Temporal Lobe Epilepsy.

Introduction: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue. Methods: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15). Results: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy. Conclusion: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.

Pulmonary histopathology in fatal paraquat poisoning.

Paraquat is a potent herbicide widely used in the Indian agriculture industry. Human fatality due to paraquat poisoning is not uncommon in this country. The primary effect of paraquat is on the lungs, and the resultant pulmonary damage leads to the patient's demise. There is a high mortality rate in paraquat poisoning as the treatment is usually supportive with no known antidote. There are limited human studies that have observed the histopathological changes in lungs in paraquat poisoning. The authors have discussed the time-related histopathological changes in lungs in paraquat poisoning on autopsy subjects. The role of anticoagulants and fibrinolytic agents in the treatment of this poisoning has also been discussed.

Blunt-chest-trauma-induced acute myocardial infarction.

Blunt chest trauma (BCT) is one of the rarest causes of acute myocardial infarction (AMI). This paper reports the case of a young married man who suffered from AMI due to BCT sustained in a fight with his wife. The histopathology examination revealed a rupture of atherosclerotic plaque with superimposed thrombus in the proximal left anterior descending artery. This report also reviews previously reported BCT-induced AMI cases in the literature.

Invasive pulmonary aspergillosis with brain dissemination in an immunocompetent host.

Invasive aspergillosis is an uncommon infection, which is mainly seen among immunocompromised patients. In recent years, cases of aspergillosis involving immunocompetent hosts are increasingly being reported. Herein, we report the case of a 27-year-old man with fever, productive cough, shortness of breath, and left hemiparesis. He had suffered trauma to his head 25 days prior. Imaging of the chest showed bilateral cavitary lesions in the lungs, and neuroimaging revealed a space-occupying lesion in the right frontoparietal cerebrum. He was suspected of having an abscess or metastasis. He died on day 3 of hospitalization, and an autopsy was performed. The autopsy revealed the cause of death to be invasive pulmonary aspergillosis, with brain dissemination. Invasive aspergillosis is uncommon in apparently immunocompetent individuals, and we discuss the autopsy findings in detail.

Invasive pulmonary aspergillosis with brain dissemination in an immunocompetent host

Invasive aspergillosis is an uncommon infection, which is mainly seen among immunocompromised patients. In recent years, cases of aspergillosis involving immunocompetent hosts are increasingly being reported. Herein, we report the case of a 27-year-old man with fever, productive cough, shortness of breath, and left hemiparesis. He had suffered trauma to his head 25 days prior. Imaging of the chest showed bilateral cavitary lesions in the lungs, and neuroimaging revealed a space-occupying lesion in the right frontoparietal cerebrum. He was suspected of having an abscess or metastasis. He died on day 3 of hospitalization, and an autopsy was performed. The autopsy revealed the cause of death to be invasive pulmonary aspergillosis, with brain dissemination. Invasive aspergillosis is uncommon in apparently immunocompetent individuals, and we discuss the autopsy findings in detail.

Blunt-chest-trauma-induced acute myocardial infarction

Blunt chest trauma (BCT) is one of the rarest causes of acute myocardial infarction (AMI). This paper reports the case of a young married man who suffered from AMI due to BCT sustained in a fight with his wife. The histopathology examination revealed a rupture of atherosclerotic plaque with superimposed thrombus in the proximal left anterior descending artery. This report also reviews previously reported BCT-induced AMI cases in the literature.

Pulmonary histopathology in fatal paraquat poisoning

Paraquat is a potent herbicide widely used in the Indian agriculture industry. Human fatality due to paraquat poisoning is not uncommon in this country. The primary effect of paraquat is on the lungs, and the resultant pulmonary damage leads to the patient's demise. There is a high mortality rate in paraquat poisoning as the treatment is usually supportive with no known antidote. There are limited human studies that have observed the histopathological changes in lungs in paraquat poisoning. The authors have discussed the time-related histopathological changes in lungs in paraquat poisoning on autopsy subjects. The role of anticoagulants and fibrinolytic agents in the treatment of this poisoning has also been discussed.

Prevalence of Atherosclerotic Coronary Stenosis in Asymptomatic North Indian Population: A Post-mortem Coronary Angiography Study.

AIM: A preliminary study of coronaries using post-mortem angiography was undertaken to see the prevalence of atherosclerotic coronary stenosis in non-cardiac unnatural deaths. MATERIALS AND METHODS: This study was conducted in a tertiary care centre located in Chandigarh. A total of 128 medico-legal cases were studied comprising 88 males and 40 females. Post-mortem examinations of these MLC cases were conducted in the Department of Forensic Medicine, PGIMER, Chandigarh. All hearts were visually screened by post-mortem coronary angiography first and then grossly examined using serial transverse incision technique in positive screening cases to find the degree of narrowing. RESULTS: Of the study group, 34% males and 20% females showed evidence of narrowing on angiography. Of the males showing coronary stenosis, 83% had single vessel disease and 13% had double vessel disease, while only one individual had triple vessel disease. In cases of female, all the cases of coronary stenosis were single vessel disease. Left anterior descending coronary artery (LAD) was the most common vessel involved, followed by right coronary artery (RCA) & Left circumflex artery (LCX) and in cases of double vessel disease, LAD in combination with LCX was responsible for 75% of the cases. Remarkably 23.6% of study population in the age group of less than 40 years showed appreciable narrowing in at least one of the coronaries. CONCLUSION: In general, the prevalence of CAD is on the rise, particularly in younger population owing to the changes in their lifestyle and food habits. This preliminary study revealed evidence of narrowing of at least one coronary in 34% male and 20% female population and 23.6% subjects were less than 40 years old. Further detailed studies are needed especially in younger age group and to support the need for preventive cardiology in the early years of life.

Intrauterine Fetal Death in Gunshot Injury to the Gravid Uterus: Forensic Perspective.

Assault on pregnant women is not a rare event; however forensic analysis of gunshot injuries among the same group requires a greater deliberation. This is the report of a 38-week-old fetus which succumbed following gunshot injuries to the mother while the latter survived. The uniqueness of fetal injuries in the form of avulsed wound with complete detachment of anus is of great forensic interest. Such unusual wound pattern could have been the result of a blast wave effect created due to the high velocity projectile affecting the fluid filled uterine cavity.

Alcohol and Drug Use in Injured Drivers - An Emergency Room Study in a Regional Tertiary Care Centre of North West India.

BACKGROUND: Statistics show an increasing proportion of alcohol and drug use in drivers in more recent times throughout the world. It has been found that among the various human factors, alcohol consumption, using drugs and subsequent driving on the roads are major risk factors. Traffic regulations in India penalises drivers who drive beyond permissible alcohol limit of 30 mg%. Consumption of psychoactive drugs such as opioid, cannabis and benzodiazepines has been reported mainly among youngsters. Hardly any data is available in Indian context particularly from North-West Zone of India. STUDY OBJECTIVE: To study the pattern of alcohol, opioid, cannabis and benzodiazepines use in injured drivers presenting to a designated trauma centre in Chandigarh zone of North-West India. MATERIALS AND METHODS: Consenting injured drivers who presented to the trauma centre in Chandigarh from September 2013 to January 2014 were included. Urine samples collected from the subjects were screened for abusive drug exposure (opioid, cannabis and benzodiazepines) and alcohol using commercial bedside urine immunoassay kits. In urine alcohol positive cases blood samples were collected and analysed for alcohol concentration using standard gas chromatography. Retrograde extrapolation method was used to assess BAC at the time of accident. RESULTS: A total of 200 injured drivers were included in this study. We found substance consumption in 54.5% of drivers and alcohol (40.5%) was the most prevalent substance consumed followed by opiates (13%), cannabis (7%) and benzodiazepines (7%). More than one substance was shown in urine of 11.5% of drivers. Among 81 alcohol positive screening cases, the quantitative analysis was successfully done for 76 cases. Except one, all cases showed BAC value more than 30 mg% which is the legal limit for driving any vehicle in India. The values of alcohol concentration in blood at the time of accident were in the range of 20 to 391 mg%. CONCLUSION: This study has shown that drivers are consuming not only alcohol but other psychoactive drugs also. Indian traffic regulatory authorities are penalising drunk drivers by doing road side breath alcohol testing with no protocols for drug screening. Appropriate measures should be adopted to screen traffic offenders for psychoactive drugs also.

Effect of aceclofenac on pharmacokinetic of phenytoin.

Aceclofenac is presently most commonly prescribed analgesic for chronic pain and inflammatory conditions. In clinical practice, phenytoin and aceclofenac are used in a chronic condition of generalized seizure with concomitant chronic pain. Hence there are chances of drug-drug interaction because modulations of isoenzymes involved in metabolism of phenytoin and aceclofenac are CYP2C9/10 and CYP2C19. It is important to maintain the therapeutic level of phenytoin in plasma for effective control of seizure. So, the aim of the study was to determine the effect of aceclofenac on the pharmacokinetics of phenytoin in rabbits. In a parallel design study, phenytoin 30 mg/kg/day per oral was given daily for seven days. On day 7, blood samples were taken at various time intervals between 0-24 hours. In aceclofenac group, phenytoin was administered for seven days as above. On day 8, aceclofenac 14 mg/kg along with phenytoin 30 mg/kg/day was administered and blood samples drawn as above. Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated. In aceclofenac group, there was decrease in t½el than phenytoin group significant changes were observed in the pharmacokinetic parameters in aceclofenac treated group. These results suggest that aceclofenac alter the pharmacokinetics of phenytoin. Confirmation of these results in human studies will warrant changes in phenytoin dose or frequency when aceclofenac is co-administered with it.