Anti-apoptotic and antioxidant mechanisms may underlie the abrogative potential of Ocimum gratissimum Linn. Leaf extract and fractions against trastuzumab-induced cardiotoxicity in Wistar rats.

Clinical use of trastuzumab (TZM), has been widely associated with increased incidence of cardiotoxicity. Ocimum gratissimum Linn. is a household medicinal plant popularly used for treating inflammatory conditions. In this study, we investigated the abrogative potential of 100 mg/kg/day of the ethanol leaf extract of Ocimum gratissimum Linn. (OG) and its petroleum ether (PEOG), ethyl acetate (EAOG) and ethanol (EOG) fractions in TZM intoxicated Wistar rats for 7 days using anthropometric, biochemical, histopathological and immunohistochemical endpoints. In addition, secondary metabolite constituents in OG and its fractions were determined through Gas Chromatography-Mass Spectrometry (GC-MS). The study results showed that oral pretreatments with OG and OG fractions as well as the fixed dose valsartan-lisinopril (VAL-LSP) combination effectively ameliorated and restore nearly normal levels the TZM-altered plasma cardiac troponin I and antioxidant profile which were corroborated by histopathological and immunohistochemical findings as indicated by the inhibition of TZM-induced activation of caspases-3 and - 9 and profound upregulation of BCL-2 expression. Phytoscan of OG and its fractions showed the presence of thymol and in high amount. Overall, our findings revealed the cardioprotective potentials of OG, OG fractions and fixed dose VAL-LSP combination against TZM-induced cardiotoxicity which probably was mediated via abrogation of cardiomyocyte apoptosis and antioxidant mechanisms.

Oxidized dietary lipids induce vascular inflammation and atherogenesis in post-menopausal rats: estradiol and selected antihyperlipidemic drugs restore vascular health in vivo.

BACKGROUND: Thermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when eaten. Consumption of thermoxidized oil in post-menopausal conditions where the estrogen level is low contributes to cardiovascular disease. This study evaluates the role of estradiol and antihyperlipidemic agents (AHD) in restoring the vascular health of ovariectomized (OVX) rats fed with thermoxidized palm oil (TPO) and thermoxidized soya oil (TSO) diets. METHOD: A total of 10 groups of rats (n = 6) were set up for the experiment. Group I (normal control) rats were sham handled while other groups were OVX to bring about estrogen deficient post-menopausal state. Group II (OVX only) was not treated and received normal rat chow. Groups III-X were fed with either TPO or TSO diet for 12 weeks and treated with estradiol (ETD) 0.2 mg/kg/day, atorvastatin (ATV) 10 mg/kg/day, and a fixed-dose combination of ezetimibe and ATV (EZE 3 mg/kg/day + ATV 10 mg/kg/day). RESULTS: Pro-atherogenic lipids levels were significantly elevated in untreated TSO and TPO groups compared to OVX and sham, resulting in increased atherogenic and Coronary-risk indices. Treatment with Estradiol and AHDs significantly reduced the total cholesterol, triglycerides, low-density lipoprotein cholesterol as well as AI and CRI compared to untreated TSO and TPO groups, whereas TSO and TPO groups showed significant elevation in these parameters compared to Group I values. Moreover, aortic TNF-α levels were extremely elevated in the untreated TSO and TPO compared to Group I. TNF-α levels were significantly reduced in rats treated with AHDs and ETD. Localized oxidative stress was indicated in the aortic tissues of TSO and TPO-fed OVX rats by increased malondialdehyde and decreased glutathione, catalase, and superoxide dismutase levels. This contributed to a depletion in aortic nitric oxide. AHDs and ETD replenished the nitric oxide levels significantly. Histological evaluation of the aorta of TSO and TPO rats revealed increased peri-adventitia fat, aortic medial hypertrophy, and aortic recanalization. These pathologic changes were less seen in AHDs and ETD rats. CONCLUSION: This study suggests that ETD and AHDs profoundly attenuate oxidized lipid-induced vascular inflammation and atherogenesis through oxidative-stress reduction and inhibition of TNF-α signaling.

Trends in motorcycle accident mortality in Lagos: Consequences of government policy changes.

Background: Motorcycle use is associated with fatal crashes. The government of Lagos State, Nigeria has introduced legislation and policies to address this issue. Aim: To examine trends in motorcycle accident mortality in Lagos over a 10-year period (January 2010 - December 2019) and consider the impact of transportation legislation and policy changes on deaths from motorcycle accidents during that period. Method: A retrospective analysis of all autopsies performed on decedents from motorcycle crashes between January 2010 and December 2019. Results: There were 211 cases of motorcycle accident-related deaths. Most victims were males (89.1%), the peak age was 31-40 years (30.8%), and majority were riders and pillion passengers (39.8% each). Head injury (51.6%) was the most common injury and cause of death. There was a general decline in case numbers from 2010 to 2019. Following new legislation that introduced a motorcycle hailing service between 2017 and 2019, there was a 17.4% reduction in fatalities from accidents. Conclusion: There has been a general downward trend in fatal motorcycle accidents in Lagos from 2010 to 2019. Changes in government transportation policies have likely had consequences on motorcycle accident-related mortality.

Right ventricular dysplasia in the elderly: a case report from autopsy.

Right ventricular dysplasia (RVD) is a rare disease of the heart that primarily affects the right ventricle. It is a clinical and pathological entity that presents classically with palpitations, syncope, or even sudden death. It presents rarely in the elderly. Where sudden death is the first and only presentation, an autopsy is required to make the diagnosis. However, the pathomorphological features of RVD can easily be overlooked or missed at autopsy. We report the case of a 68-year-old male with the past medical history of hypertension, gout and inflammatory bowel syndrome. He was admitted on account of difficulty in breathing, abdominal swelling and reduced urination. Physical examination revealed hypertension with cardiac murmurs, widespread crepitations, distended abdomen and lower limb oedema. Provisional diagnoses of acute-on-chronic kidney disease and congestive cardiac failure secondary to hypertensive heart disease, precipitated by probable gastrointestinal infection were made. While on admission, he had an episode of syncope. Electrocardiogram revealed bigeminy and bradycardic sinus rhythm with unifocal ventricular premature contraction. He died on the 8th week of admission. Autopsy revealed an enlarged heart weighing 600gm; there was thinning of the apical aspect of the right ventricular wall with subtotal fibrofatty replacement. Microscopic examination revealed a transmural replacement of cardiac myocytes by fibroadipose tissue extending inwards, in the most parts, from the epicardium to the endocardial surface. Our aim is to increase the awareness of these pathomorphological features among anatomic/forensic pathologists.

Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity.

Trastuzumab (TZM) is useful in the clinical management of HER2-positive metastatic breast, gastric, and colorectal carcinoma but has been limited by its off-target cardiotoxicity. This study investigates the therapeutic potentials of 0.25 mg/kg/day amlodipine, 0.035 mg/kg/day lisinopril, 5 mg/kg/day valsartan, and their fixed-dose combinations in TZM-intoxicated Wistar rats that were randomly allotted into 10 groups of 6 rats for each group. Group I rats were treated with 10 ml/kg/day sterile water orally and 1 ml/kg/day sterile water intraperitoneally; Groups II, III, and IV rats were orally gavaged with 5 mg/kg/day valsartan and 1 ml/kg/day sterile water intraperitoneally, 0.25 mg/kg/day amlodipine and 1 ml/kg/day sterile water via the intraperitoneal route, 0.035 mg/kg/day lisinopril and 1 ml/kg/day sterile water administered intraperitoneally, respectively. Group V rats were orally treated with 10 ml/kg/day of sterile water prior to intraperitoneal administration of 2.25 mg/kg/day of TZM. Groups VI-VIII rats were equally pretreated with 5 mg/kg/day valsartan, 0.25 mg/kg/day amlodipine, and 0.035 mg/kg/day lisinopril before intraperitoneal 2.25 mg/kg/day TZM treatment, respectively; Groups IX and X rats were orally pretreated with the fixed-dose combinations of 0.25 mg/kg/day amlodipine +0.035 mg/kg/day lisinopril and 5 mg/kg/day valsartan +0.035 mg/kg/day lisinopril, respectively, before TZM treatment. Cardiac injury and tissue oxidative stress markers, complete lipids profile, histopathological, and immunohistochemical assays were the evaluating endpoints. Results showed that repeated TZM treatments caused profound increases in the serum TG and VLDL-c levels, serum cTnI and LDH levels, and cardiac tissue caspase-3 and -9 levels but decreased BCL-2 expression. TZM also profoundly attenuated CAT, SOD, GST and GPx activities, and increased MDA levels in the treated tissues. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, the altered biochemical, histopathological, and immunohistochemical changes were reversed with amlodipine, lisinopril, valsartan, and fixed-dose combinations, although fixed-dose valsartan/lisinopril combination was further associated with hyperlipidemia and increased AI and CRI values and coronary artery cartilaginous metaplasia. Thus, the promising therapeutic potentials of amlodipine, lisinopril, valsartan and their fixed-dose combinations in the management of TZM cardiotoxicity, majorly mediated via antiapoptotic and oxidative stress inhibition mechanisms were unveiled through this study.

Hypertension and Sudden Unexpected Deaths: An Autopsy Study of Four Hundred and Seventy-Seven Brought-in-Dead in a Tertiary Health Center.

INTRODUCTION: Hypertension is an important and major public health concern globally. One of the major causes of sudden death worldwide is hypertension. This study is to present the morphological pattern of deaths at autopsy of those patients who were brought-in-dead (BID) and who had hypertensive heart disease (HHD) as the underlying illness. MATERIALS AND METHODS: This is a 6-year retrospective autopsy study of BID patients as a result of HHD seen at our department between January 1, 2010, and December 31, 2015. The autopsy findings and data retrieved were analyzed using IBM Statistical Package for Social Sciences version 20. Test for statistical significance was set at P < 0.05. RESULTS: A total of 477 deaths (44%) as a result of HHD were recorded out of the 1016 BID during the period under study. The age ranged from 21 to 92 years with a mean age of 52 ± 14.0 years and a male to female ratio of 1.8:1. The 5th decade of life was the most common age group encountered. The most common cause of death was acute left ventricular failure (67.8%), and myocardial infarction was the least common (1.7%). CONCLUSIONS: Acute left ventricular heart failure was the most common cause of sudden death as a result of hypertension and was followed by intracerebral hemorrhage. In the female gender, sudden deaths were most common in the 6th decade and in the male gender most sudden deaths were seen in the 5th decade.

Forensic odontological observations in the victims of DANA air crash.

INTRODUCTION: Forensic odontology or forensic dentistry is that aspect of forensic science that uses the application of dental science for the identification of unknown human remains and bite marks. Deaths resulting from mass disasters such as plane crash or fire incidence have always been given mass burial in Nigeria. This was obviously due to the fact that Forensic Pathologists whose roles involve disaster victim identification were not available at that time. However, in the DANA air crash in Lagos in 2012, the Forensic pathologist and dental teams were invited for the first time to identify the victims. The objectives of this paper are to identify the extent of victims' identification using Forensic odontology alone and its combination with DNA analysis. It also presents the pattern of fractures seen in the mandible and maxilla of the victims. METHODS: The bodies were dissected using following the standard protocol dissection. Prior to this all the victims had Dental Radiological Examination. The oral cavities were exposed after which the Odontology team was invited for photographing first, followed by dental charting. Fractures of the mandible, maxilla including the anatomical regions were all recorded and photographed. Dental prosthesis, restorations, crowns and bridge and other findings were also noted, recorded and compared with ante mortem records where available. RESULTS: A total of 152 bodies were recovered from the crash site while 148 victims were eventually identified through a combination of DNA analysis and forensic odontology. This represented 97.4%. Forensic odontology was the primary identifier in 10%. There were no fingerprinting information in this country at present therefore, it could not be used. A total of 89 (60%) were males while females accounted for 59(40%). This gives a ratio of 1.5:1. Most of the victims were in the age group 30-49 years; this represented 52% of the victims while the least involved age groups were victims above 60 years of age which accounted for only 4.7%. Mandibular fractures were seen in 29 victims, maxilla in 15, combined mandibullo/maxillary in 15 victims, while 89 victims had no jaw fracture. The most common area of fracture in the mandible was the body which accounted for 36.4%, closely followed by parasymphyseal region 31.9%, symphyseal 22.7% and the angle 9.0%. The most common fracture in the maxillae was palatal split fracture which accounted for 52%, this was followed by pterygoid 24%, alveolar 8% and multiple locations 16%. CONCLUSION: A combination of DNA analysis and forensic odontology was able to identify a total of 148 victims out of 152 representing 97.4%. Forensic odontology was the primary identifier in only 10%. In the latter, poor and lack of dental records were responsible for this very low figure. The most common area of fracture in the mandible was the body which accounted for 36.4%, while that of the maxillae was palatal fracture which accounted for 52%. Padding of the back of the seats in the aircraft should be canvassed for to provide Cushing effect for passengers.

Spectrum of intracranial tumours in a tertiary health carefacility: our findings.

INTRODUCTION: Primary brain tumours are uncommon with an annual incidence of 5-10/100000. This study has attempted to analyse the histological pattern of intracranial tumours seen in our centre. METHODS: A retrospective study of cases of intracranial tumours seen was conducted over a period of 5 years ie from January 2008 to December 2012. All the slides were reviewed. The age, sex, diagnosis using the WHO grading and the histological subtypes were recorded. Data were analysed using the (SPSS) Software version 17. RESULTS: Altogether, 56 cases of intracranial tumours were seen out of a total of 12,610 biopsies representing 0.004%. The male to female ratio (M: F) was approximately 1:1.1 The mean age of the patients was 36±20.35 (range, 2 to 85). Astrocytomas accounted for 30% (17) while 29% (16) had Meningioma. Medulloblastoma accounted for 18%. (10). Of the cases of Gliomas, majority (52%) fell under WHO grade II. (38%)of the Meningioma were of the mixed type while 25% had transitional type. CONCLUSION: Astrocytomas was the commonest brain tumour. These patterns corroborated most studies that have been done. Metastasis to the brain was however, not seen in this study.

Forensic Investigation of mass disasters in Nigeria: A review.

This paper is to establish the present state of things in the country in terms of legal framework and the availability of personnel with a view to presenting an overview of proper mass disaster investigations. This is a retrospective review of mass disasters in Nigeria that occurred within the last 20 years. The study therefore reviews the state of the forensic investigation of the mass disasters as well as the efforts made to identify the victims of the disaster. The process of proper forensic investigation from the stage of evaluation of the scene and recovery process to the final identification of victims are presented to serve as a protocol for the country. The assessment of the present state of preparedness in Nigeria is also examined with a view to improving the practice to international standards. Data were retrieved from official documents from the aviation industry as well as Nigeria news reports. The standard protocols for disaster victim identification were retrieved from the guide released by the INTERPOL. The state of preparedness of the country and recommendations for improvement are presented. The Federal government and the states of the federation should without further delay put in place the process of reviewing the law of Coroner's system and provide the enabling environment for the proper forensic investigation. The training curriculum of the first responders should incorporate mass disaster investigations in order to produce efficient officers and personnel. A functional disaster victim identification (DVI) team is strongly advocated to incorporate different professionals involved in mass disaster management.