Role of Hematological Parameters in the Early Diagnosis of Neonatal Sepsis.

The major cause of neonatal mortality and morbidity is bacterial sepsis. Blood culture is the most reliable method in neonatal sepsis. This study was conducted to study the usefulness of hematological parameters in the early diagnosis of neonatal sepsis and to assess the most sensitive and specific variables in diagnosing neonatal sepsis. This prospective study was conducted in a tertiary care hospital from January 2017 to January 2018. Peripheral blood smears were prepared from patients with clinical suspicion of sepsis or predisposing perinatal factors for sepsis and stained with Field's stain and examined. The hematological findings were analyzed according to the hematologic scoring system of Rodwell. It was found that immature PMN count, I: M ratio, and I: T ratio had the highest sensitivity (92.06%, 87.30%, and 74.60%, respectively) while I: M ratio, I: T ratio, and degenerative changes in PMN had the highest specificity (97.50%, 96.50%, and 94.0%, respectively) in the prediction of sepsis.

Correlation of Robinson's Cytological Grading with Elston and Ellis' Nottingham Modification of Bloom Richardson Score of Histopathology for Breast Carcinoma.

Introduction: Invasive carcinoma of the breast is one of the leading causes of death in women. In developing countries, fine needle aspiration cytology (FNAC) of the breast is used for preoperative diagnosis of breast cancer due to low cost. The grading system of breast carcinoma on FNAC is widely accepted. In the era of neoadjuvant therapy, if grading of breast carcinoma is incorporated in FNAC reports for prognostication, it will be of great help especially in patients with locally advanced disease, older patients with accompanying chronic disease and patients who reject surgery. Hence, there is much to be gained by grading a tumor on FNAC. Materials and methods: The present study was conducted on 40 cases of cytologically diagnosed breast carcinomas. Fine needle aspiration cytology smears were graded by Robinson cytological grading system. All surgical specimens were processed and the histological grading of the resulting slides was done by the Nottingham modification of Bloom Richardson score. Then, the cytological grade was compared with the histological grade and statistical analysis was done. Results:Based on Robinson grading method, cases were classified into grade I (15%), grade II (55%) and grade III (30%). Based on the Nottingham modification of Bloom Richardson (SBR) grading method, the cases were classified as grade I (5%) and grade II and III (47.5%) each. A total concordance rate between both the grading systems was seen in 65% of cases. A positive correlation was found and there was a significant association between Robinson cytological grading and SBR histological grading. Conclusions:Grading breast carcinoma on cytology allows its prognostic evaluation along with diagnostic value without any additional morbidity or expense to the patient. Thus, it is recommended to grade breast carcinomas on FNAC. It helps in deciding the proper line of treatment, so that patients can have a better prognosis.

Hypertensive Emergency As Initial Presentation of Systemic Sclerosis Sine Scleroderma.

Hypertensive emergency is a common cause of emergency room (ER) visits. Scleroderma renal crisis (SRC) is one of the rare causes of hypertensive emergency. SRC is a life-threatening condition that presents with acute onset severe hypertension accompanied by retinopathy, encephalopathy, and rapidly worsening renal function. We present a case of hypertensive emergency and renal failure with positive anti-Scl 70 and RNA polymerase III which is characteristic of SRC. Despite appropriate supportive care and timely treatment with angiotensin-converting enzyme inhibitors, the patient progressed to end-stage kidney disease.

Lithium-induced nephropathy; One medication with multiple side effects: a case report.

BACKGROUND: Lithium carbonate is commonly used in the treatment of bipolar disorder. A spectrum of side effects is associated with lithium, including nephrogenic diabetes insipidus, renal tubular acidosis, chronic tubulointerstitial nephropathy, and minimal change disease. Although the former three adverse effects are well-known, minimal change disease is relatively rare. CASE PRESENTATION: We herein report a case of lithium therapy-induced minimal change disease with concurrent chronic tubulointerstitial nephropathy. A 66-year old man with bipolar disorder treated by lithium for 20 years, presented to the hospital with anasarca and decreased urine output for 4 weeks. The medical history also included hyperlipidemia, hypertension, and benign prostatic hyperplasia. Further laboratory investigation revealed elevated serum lithium (2.17 mmol/L), potassium (6.0 mmol/L), and creatinine levels (2.92 mg/dL), nephrotic range proteinuria, and hypoalbuminemia. Lithium was discontinued and the patient was treated with intravenous fluids. He underwent a kidney biopsy, which showed findings consistent with minimal change disease with concurrent acute tubular injury and chronic tubulointerstitial nephropathy. The patient was subsequently treated with steroids in an outpatient setting. He did not respond to the treatment, and hemodialysis was started. CONCLUSION: Based on the previously reported cases and review of literature, occurrence of lithium-associated minimal change nephropathy is rare. Patients with lithium-associated minimal change disease and acute tubular injury usually respond to discontinuation of lithium therapy and/or steroid treatment. In this case, minimal change nephropathy was steroid-resistant and kidney function of the patient reported here did not recover after 6-month follow-up. We postulated the underlying cause to be minimal change disease with chronic tubulointerstitial nephropathy due to long-term lithium use. This case provides an example of a rare side effect of lithium-induced minimal change nephropathy with chronic tubulointerstitial nephropathy in addition to its well-known complication of interstitial nephritis or diabetes insipidus. In our opinion, these patients likely have much worse clinical outcome.

Vicinal diaryl azole-based urea derivatives as potential cholesterol lowering agents acting through inhibition of SOAT enzymes.

A novel series of vicinal diaryl azole-urea derivatives were synthesized and evaluated for their potential to inhibit SOAT enzyme. Among the reported compounds, compound (12d) emerged as the most potent compound with an IC50 value of 2.43 µM. In polaxamer-407 induced lipoprotein lipase inhibition model, compound (12d) reduced triglyceride turnover in vivo. Compound (12d) also showed dose-dependent prevention of serum total cholesterol and prevention of LDL-C elevation at a dose of 30 mg/kg. Furthermore, compound (12d) showed potential to stop falling levels of serum HDL-C dose-dependently and improved the atherogenic index. Effect of 12d on body weight, plaque formation and development of atherogenic lesions were studied. Toxicological study of compound (12d) indicated that at a dose of 2000 mg/kg, 12d was devoid of any signs of toxicity or mortality.

Comparison of different osmotic therapies in a mouse model of traumatic brain injury.

BACKGROUND: Inflammation in the affected region, increased intracranial pressure, consequent oedema and congestion contribute to the negative outcome of traumatic brain injury. Osmotic therapies are recommended for improvement in cognitive and motor functions. Aim of the present study was to evaluate the effect of osmotic therapies in a mice model of traumatic brain injury. METHODS: Experimental closed head injury was performed in adult Swiss albino mice by the weight-drop method. Different group of animals were treated with normal saline (G1), mannitol (G2), mannitol+glycerin (G3) and Neurotol (G4). Neurological Severity Score (NSS) was recorded at different time-points upto a period of six days. Effect of treatments on cerebral oedema, learning and memory function, motor function and co-ordination were evaluated by gravimetry, Morris water maze and beam walk test respectively. Histopathology was performed to evaluate the treatment effects on microscopic complications arising from primary closed head injury (CHI). RESULTS: All the treatments showed a marked improvement in the evaluated parameters as compared with the vehicle control group. It was evident that G3 and G4 had a distinct advantage over mannitol therapy. Based on the NSS score, Neurotol proved to be comparatively safe and more efficacious than either mannitol or a combination of mannitol+glycerol. The effect of Neurotol could have been enhanced by the presence of VRP011 (a Mg+2 salt). CONCLUSIONS: Neurotol is safe and exhibits better efficacy as compared with other treatments for the management of traumatic brain injury.

Protective effects of MCR-1329, a dual α1 and angII receptor antagonist, in mineralocorticoid-induced hypertension.

BACKGROUND: With the prototypical structures of losartan and prazosin as the axis of our research, MCR-1329 emerged as a potential designed multiple ligand from a series of compounds designed to possess dual antagonistic activity on the α1 and AT1 receptor. After confirming the activity of MCR-1329 in in vitro and acute in vivo models, the present study was undertaken to determine the efficacy of MCR-1329 in a mammalian test system. METHODS: A rat model of deoxycorticosterone acetate (DOCA)-salt induced renal hypertension following unilateral nephrectomy was utilized to determine the effect of MCR-1329. For mechanistic evaluations, MCR-1329 was evaluated on rat aortic strips in vitro and on rat aortic smooth muscle cells to determine the role of MCR-1329 on phosphoinositide 3 kinase (PI3K) signaling. RESULTS: Results of the study showed that MCR-1329 prevents development of arterial hypertension. It was also observed that MCR-1329 upheld the intimal structures of major arteries like the thoracic aorta. Acetylcholine (Ach)-mediated relaxation remained intact in arteries from MCR-1329 treated animals. It was observed that MCR-1329 partially prevents Thr-308 phosphorylation of Akt following ligand-mediated receptor stimulation in vascular smooth muscle cells. Addition of LY294002 to the reaction medium caused a near-complete inhibition of Akt-phosphorylation. This suggested that MCR-1329 elicits its antihypertensive role by blocking activation of receptor-mediated PI3K-Akt downstream signaling as well as through preservation of arterial integrity. CONCLUSIONS: MCR-1329 has the potential to be evaluated further for clinical development as a potential antihypertensive agent with multiple mechanisms of action.

Design, green synthesis and pharmacological evaluation of novel 5,6-diaryl-1,2,4-triazines bearing 3-morpholinoethylamine moiety as potential antithrombotic agents (.).

The aim of this research work was to investigate a series of novel 5,6-diaryl-1,2,4-triazines (3a-3q) containing 3-morpholinoethylamine side chain, and to address their antiplatelet activity by in vitro, ex vivo and in vivo methods. All compounds were synthesized by environment benign route and their structures were unambiguously confirmed by spectral data. Compounds (3l) and (3m) were confirmed by their single crystal X-ray structures. Out of all the synthesized compounds, 10 were found to be more potent in vitro than aspirin; six of them were found to be prominent in ex vivo assays and one compound (3d) was found to have the most promising antithrombotic profile in vivo. Moreover, compound (3d) demonstrated less ulcerogenicity in rats as compared to aspirin. The selectivity of the most promising compound (3d) for COX-1 and COX-2 enzymes was determined with the help of molecular docking studies and the results were correlated with the biological activity.

Comparative evaluation of HMG CoA reductase inhibitors in experimentally-induced myocardial necrosis: Biochemical, morphological and histological studies.

The present study was carried out to evaluate the protective effect of different statins on isoproterenol (ISO) induced myocardial necrosis. Atorvastatin, rosuvastatin, fluvastatin, simvastatin and pravastatin (10 mg/kg/day) were administered for 12 weeks. After pretreatment of 12 weeks myocardial necrosis was induced by subsequent injection of ISO (85 mg/kg/day, s.c.) to wistar rats. Serum biochemical parameters like glucose, lipid profile, cardiac markers and transaminases were evaluated. Animals were killed and heart was excised for histopathology and antioxidant study. Statins pretreated rats showed significant protection against ISO induced elevation in serum biochemical parameters and serum level of cardiac marker enzymes and transaminase level as compared to ISO control group. Mild to moderate protection was observed in different statins treated heart in histopathology and TTC stained sections. Result from our study also revealed that statins could efficiently protect against ISO intoxicated myocardial necrosis by impairing membrane bound enzyme integrity and endogenous antioxidant enzyme levels. Amongst all statins used, rosuvastatin and pravastatin were found to have maximum cardio-protective activity against ISO induced myocardial necrosis as compared to other statins.

Management of Hypertension-Journey from Single Drug Therapy to Multitargeted Ligand Therapy: A Clinical Overview.

Hypertension is recognized as one of the leading risk factors for human morbidity and mortality. It is a major risk factor for myocardial infarction, congestive heart failure, stroke, and endstage renal disease. The difficulty in controlling hypertension is related, at least in part, to the complex pathogenesis of hypertension. In spite of the availability of variety of antihypertensive agents, the control of blood pressure in the general population is at best inadequate. It is being recognized that a balanced modulation of several targets can provide a superior therapeutic effect to side effect profile compared to the use of a selective ligand. Fixed combinations of drugs and multitargeted ligands provide answers to the problem of hypertension. This review provides a status report of current antihypertensive drug therapy with fixed combination of drugs and evolvement of multitargeted ligands for better management of the disease.

Carboplatin-induced Fanconi-like syndrome in rats: amelioration by pentoxifylline.

INTRODUCTION: Carboplatin is a congener of cisplatin used in the treatment of ovarian, head and neck and small-cell lung cancer. However, the clinical efficacy of carboplatin is marred by the development of ROS-dependent nephrotoxicity. The pathophysiological damage inflicted upon the kidney by carboplatin closely resembles to that of Fanconi syndrome. AIMS AND OBJECTIVES: The present study aimed at inducing Fanconi-like syndrome in rats by administration of carboplatin. Objectives of the study involved evaluation of biochemical parameters coherent to Fanconi-like syndrome. Further, an attempt was made to evaluate the potential therapeutic effect of pentoxifylline in this condition. RESULTS: The results of the study demonstrated that the urinary excretion profile of carboplatin treated rats closely resembled to that of patients suffering from Fanconi-like condition. Pentoxifylline was able to ameliorate this nephrotoxic condition as suggested by the change in levels of membrane bound ATPases, MDA and GSH. The urinary levels of tyrosine and cysteine correlate well with that of Fanconi-like condition in animals and humans. CONCLUSION: In lieu of these observations, our study suggested that carboplatin-induced renovascular damage resembles to Fanconi-like condition which can be mitigated by pentoxifylline.

Doxorubicin mediated cardiotoxicity in rats: protective role of felodipine on cardiac indices.

Anthracyclines find vital uses in the treatment of solid tumors and other kind of malignancies. A typical side effect observed with few agents of this class is dose-dependent cardiotoxicity. Doxorubicin is one such agent which backs the generation of free radicals through metabolism of its quinone structure. This effect combined with induction of apoptotic and necrotic pathways leads to the development of irreversible cardiotoxicity. Reports showing the cardioprotective effects of felodipine have been published in the past. We chose to evaluate protective effect of felodipine in acute cardiotoxicity in rats induced by single dose of doxorubicin. Felodipine was assessed against doxorubicin-induced cardiotoxicity and we found that felodipine not only improves cardiac marker enzymes (P<0.001 for LDH; P<0.01 for CK-MB) but also prevents damage to myocardial tissue (20.61% necrosed area in doxorubicin intoxication; 11.52% necrosed area in felodipine treated group). Activation of apoptotic pathways is decelerated which is indicated by a significant reduction in myocardial caspase-3 activity (P<0.05) following felodipine pretreatment. Felodipine pretreatment was able to maintain normal cardiac morphology and histoarchitecture. Gravimetric analysis revealed beneficial effects following felodipine pretreatment. Abnormalities seen in the ECG after doxorubicin treatment were normalized to a significant extent (ST interval normalization was significant at P<0.01) in felodipine treated rats. In itself, felodipine was not found to have any detrimental effects on the myocardium or hemodynamic parameters of rats. Findings of the study suggest that pretreatment with felodipine prevents doxorubicin induced cardiotoxicity.

ACAT inhibitors: the search for novel cholesterol lowering agents.

Increased level of serum cholesterol (hyperlipidemia) is the most significant risk factor for the development of atherosclerosis. Cholesterol levels are affected by factors such as rate of endogenous cholesterol synthesis, biliary cholesterol excretion and dietary cholesterol absorption. Acyl CoA: Cholesterol O-acyl transferases (ACAT) are a small family of enzymes that catalyze cholesterol esterification and cholesterol absorption in intestinal mucosal cells and maintain the cholesterol homeostasis in the blood. Inhibition of the ACAT enzymes is one of the attractive targets to treat hyperlipidemia. Literature survey shows that structurally diverse compounds possess ACAT inhibitory properties. In this review, a comprehensive presentation of the literature on diverse ACAT inhibitors has been given.

Cardio protective effect of Coriandrum sativum L. on isoproterenol induced myocardial necrosis in rats.

The preventive effect of Coriandrum sativum L. (CS) on cardiac damage was evaluated by Isoproterenol (IP) induced cardiotoxicity model in male Wistar rats. Rats were pretreated with methanolic extract of CS seeds at a dose of 100, 200 or 300 mg/kg orally for 30 days and they were subsequently administered (s.c.) with IP (85 mg/kg body weight) for the last two days. IP treated rats showed increased LPO, decreased levels of endogenous antioxidants and ATPases in the cardiac tissue together with increased plasma lipids and markers of cardiac damage. TTC staining showed increased infarct areas while HXE staining showed myofibrillar hypertrophy and disruption. CS (200 and 300 mg/kg body weight) pretreatment significantly prevented or resisted all these changes. Our results show that methanolic extract of CS is able to prevent myocardial infarction by inhibiting myofibrillar damage. It is also concluded that, the rich polyphenolic content of CS extract is responsible for preventing oxidative damage by effectively scavenging the IP generated ROS.

Adipocytokines: The pied pipers.

Even though there have been major advances in therapy, atherosclerosis and coronary artery disease retain their lead as one of the major causes of morbidity and mortality in the first decade of 21(st) century. To add to the woes, we have diabetes, obesity and insulin resistance as the other causes. The adipose tissue secretes several bioactive mediators that influence inflammation, insulin resistance, diabetes, atherosclerosis and several other pathologic states besides the regulation of body weight. These mediators are mostly proteins and are termed "adipocytokines". Adiponectin, resistin, visfatin, retinol binding protein-4 (RBP-4) and leptin are a few such proteins. Adiponectin is a multimeric protein, acting via its identified receptors, AdipoR1 and AdipoR2. It is a potential biomarker for metabolic syndrome and has several antiinflammatory actions. Adiponectin increases insulin sensitivity and ameliorates obesity. Resistin, another protein secreted by the adipose tissue, derived its name due to its involvement in the development of insulin resistance. It plays a role in the pathophysiology of several conditions because of its robust proinflammatory activity mediated through the activation of extracellular signal regulated kinases 1 and 2 (ERK 1/2). In 2007, resistin was reported to have protective effect in ischemia-reperfusion injury and myocyte-apoptosis in the setting of myocardial infarction (MI). RBP-4 is involved in the developmental pathology of type 2 diabetes mellitus and obesity. Visfatin has been described as an inflammatory cytokine. Increased expression of visfatin mRNA has been observed in inflammatory conditions like atherosclerosis and inflammatory bowel disease. Leptin mainly regulates the food intake and energy homeostasis. Leptin resistance has been associated with development of obesity and insulin resistance. Few drugs (thiazolidinediones, rimonabant, statins, etc.) and some lifestyle modifications have been found to improve the levels of adipocytokines. Their role in therapy has a lot in store to be explored upon.

Effect of vitamin E alone and in combination with lycopene on biochemical and histopathological alterations in isoproterenol-induced myocardial infarction in rats.

BACKGROUND: The present study has been designed to evaluate the combined cardioprotective effect of vitamin E and lycopene on biochemical and histopathological alteration in isoproterenol-induced myocardial infarction in rats. MATERIALS AND METHODS: Adult male albino rats of Wistar strain were treated with isoproterenol (200 mg/kg, s.c.) for 2 days at an interval of 24 h to develop myocardial infarction. Vitamin E (100 mg/kg/day, p.o.) and lycopene (10 mg/kg/day, p.o.) were administered alone and in combination for 30 days. Change in body weight and organ weight were monitored. Levels of serum marker enzymes (AST, ALT, LDH and CK-MB), lipid peroxidation, endogenous antioxidants (GSH, GPX, GST, SOD and CAT), membrane bound enzymes (Na(+)/K(+) ATPases, Mg(2+) ATPases and Ca(2+) ATPases) were evaluated. LDH isoenzyme separation was carried out using gel electrophoresis. Histopathology of heart tissue was performed. RESULTS: Induction of rats with isoproterenol resulted in a significant elevation in organ weight, lipid peroxidation, serum marker enzymes (AST, ALT, CK-MB and LDH), and Ca( 2+) ATPases, whereas it caused a significant (P < 0.001) decrease in body weight, activities of endogenous antioxidants (GSH, GP(x), GST, SOD and CAT), Na(+)/K(+) and Mg(2+) ATPases. ISO treated rats showed high intensity band of LDH1-LDH2 isoenzymes. Treatment with the combination of Vitamin E and lycopene for 30 days significantly attenuated these changes as compared to the individual treatment and ISO treated groups. Histopathological observations were also in correlation with the biochemical parameters. CONCLUSION: These findings indicate the synergistic cardioprotective effects of vitamin E and lycopene during ISO-induced myocardial infarction in rats.

Stacked generalization for early diagnosis of Alzheimer's disease.

The diagnosis of Alzheimer's disease (AD) at an early stage is a major concern due to growing number of elderly population affected by the disease, as well as the lack of a standard diagnosis procedure available to community clinics. Recent studies have used wavelets and other signal processing methods to analyze EEG signals in an attempt to find a non-invasive biomarker for AD. These studies had varying degrees of success, in part due to small cohort size. In this study, multiresolution wavelet analysis is performed on event related potentials of the EEGs of a relatively larger cohort of 44 patients. Particular emphasis was on diagnosis at the earliest stage and feasibility of implementation in a community health clinic setting. Extracted features were then used to train an ensemble of classifiers based stacked generalization approach. We describe the approach, and present our promising preliminary results.