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.

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.

African Vegetables (Clerodendrum volibile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab-Induced Cardiotoxicity in Wistar Rats.

Trastuzumab (TZM) is a humanized monoclonal antibody that has been approved for the clinical management of HER2-positive metastatic breast and gastric cancers but its use is limited by its cumulative dose and off-target cardiotoxicity. Unfortunately, till date, there is no approved antidote to this off-target toxicity. Therefore, an acute study was designed at investigating the protective potential and mechanism(s) of CVE and IGE in TZM-induced cardiotoxicity utilizing cardiac enzyme and oxidative stress markers and histopathological endpoints. 400 mg/kg/day CVE and IGE dissolved in 5% DMSO in sterile water were investigated in Wistar rats injected with 2.25 mg/kg/day/i.p. route of TZM for 7 days, using serum cTnI and LDH, complete lipid profile, cardiac tissue oxidative stress markers assays, and histopathological examination of TZM-intoxicated heart tissue. Results showed that 400 mg/kg/day CVE and IGE profoundly attenuated increases in the serum cTnI and LDH levels but caused no significant alterations in the serum lipids and weight gain pattern in the treated rats. CVE and IGE profoundly attenuated alterations in the cardiac tissue oxidative stress markers' activities while improving TZM-associated cardiac histological lesions. These results suggest that CVE and IGE could be mediating its cardioprotection via antioxidant, free radical scavenging, and antithrombotic mechanisms, thus, highlighting the therapeutic potentials of CVE and IGE in the management of TZM-mediated cardiotoxicity.

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.

Giant Solitary Anterior Cervical Canal Neurofibroma: Case Report and Surgical Technique.

Giant solitary anterior cervical canal neurofibroma (GSACCN) is rarely reported in the literature. When the large lesion is ventrally located to the spinal cord, an anterolateral approach may not be ideal due to various technical challenges. In this report, we describe a case of intradural extramedullary GSACCN located at the cervical region extending from the axis to the sixth cervical vertebrae. Here we also describe a posterior technique successfully used to resect the tumour. Therefore, the posterior approach by En bloc decompressive laminectomy and laminoplasty might be used to adequately treat the lesion.

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.