Update on quetiapine in the treatment of bipolar disorder: results from the BOLDER studies

The essential features of bipolar affective disorder involve the cyclical occurrence of high (manic or hypomanic episodes) and low mood states. Depressive episodes in both bipolar I and II disorder are more numerous and last for longer duration than either manic or hypomanic episodes. In addition depressive episodes are associated with higher morbidity and mortality. While multiple agents, including all 5 atypical antipsychotics, have demonstrated efficacy and earned US FDA indication for manic phase of bipolar illness, the acute treatment of bipolar depression is less well-studied. The first treatment approved by the US FDA for acute bipolar depression was the combination of the atypical antipsychotic olanzapine and the antidepressant fluoxetine. Recently, quetiapine monotherapy has demonstrated efficacy in the treatment of depressive episodes associated with both bipolar I and II disorder and has earned US FDA indication for the same.     

Activation of the abundant nuclear factor poly(ADP-ribose) polymerase-1 by Helicobacter pylori

Modification of eukaryotic proteins is a powerful strategy used by pathogenic bacteria to modulate host cells during infection. Previously, we demonstrated that Helicobacter pylori modify an unidentified protein within mammalian cell lysates in a manner consistent with the action of a bacterial ADP-ribosylating toxin. Here, we identified the modified eukaryotic factor as the abundant nuclear factor poly(ADP-ribose) polymerase-1 (PARP-1), which is important in the pathologies of several disease states typically associated with chronic H. pylori infection. However, rather than being ADP-ribosylated by an H. pylori toxin, the intrinsic poly(ADP-ribosyl) polymerase activity of PARP-1 is activated by a heat- and protease-sensitive H. pylori factor, resulting in automodification of PARP-1 with polymers of poly(ADP-ribose) (PAR). Moreover, during infection of gastric epithelial cells, H. pylori induce intracellular PAR-production by a PARP-1-dependent mechanism. Activation of PARP-1 by a pathogenic bacterium represents a previously unrecognized strategy for modulating host cell signaling during infection.     

Antiepileptic Drugs in Mood-Disordered Patients

Summary:  Bipolar disorder is a common, recurrent, often severe mental disorder that, without adequate treatment, is associated with high rates of morbidity and mortality. We review the evidence on the efficacy of a spectrum of antiepileptic drugs (AED) in bipolar disorder. Most studies have been carried out with carbamazepine (CBZ), valproate (VPA), and lamotrigine (LTG). All three of these AEDs have been shown to be of value in the management of patients with bipolar illnesses. VPA and CBZ seem to exert stronger antimanic effects and, to a lesser degree, acute antidepressant efficacy. LTG seems to be effective against depression and mania, with a more robust activity against depression. No firm evidence supports a role for vigabatrin, tiagabine, topiramate, or levetiracetam in these disorders.     

Long-term treatment with neutral endopeptidase inhibitor improves cardiac function and reduces natriuretic peptides in rats with chronic heart failure

OBJECTIVE: Increased secretion of atrial and brain natriuretic peptide (ANP and BNP) from hearts is known to exhibit favorable effects in patients and animals with heart failure, and inhibition of neutral endopeptidase (NEP), an enzyme that degrades ANP and BNP, may further increase these peptide levels. However, it is still unknown whether such elevation of the ANP and BNP may offer a therapeutic benefit to the progression of chronic heart failure (CHF). We examined the effects of ONO-9902, a novel NEP inhibitor, on changes in hemodynamic parameters, NEP activity and neurohumoral factors in rats with CHF induced by left coronary artery ligation (CAL). METHODS: Male Wistar rats (220-240 g) were subjected to induction of acute myocardial infarction by CAL. Rats were orally treated with ONO-9902 (300 mg/kg/day) from the 1st to 6th week after the operation. Hemodynamic and/or biochemical assessments were performed at the 1st and 6th weeks after the operation. RESULTS: A single administration of ONO-9902 inhibited the plasma and kidney NEP activities and thereby further augmented the elevation of plasma ANP concentration in rats with CAL at the 1st week after the operation. In rats with CAL at the 6th week after the operation, the left ventricular end-diastolic pressure (LVEDP) increased and cardiac output index (COI) decreased as compared with those of sham-operated rats. These changes were accompanied by marked increases in the plasma ANP, BNP and endothelin-1 (ET-1). Chronic treatment with ONO-9902 attenuated the increase in LVEDP and the decrease in COI. These changes were associated with a decrease in plasma ANP, BNP and ET-1 concentrations. CONCLUSIONS: The results suggest that chronic treatment with NEP inhibitor improves depressed cardiac function in rats with CHF. ONO-9902 may offer a new and possible therapeutic approach in patients with CHF.     

Urine PGE-M: A metabolite of prostaglandin E2 as a potential biomarker of advanced colorectal neoplasia.

BACKGROUND & AIMS: The enzyme cyclooxygenase-2 is expressed in a majority of colorectal carcinomas (CRCs) and is important in prostaglandin production. We have developed an accurate method to measure the urinary metabolite of prostaglandin E(2) (PGE-M) using recently developed mass spectrometric techniques. The purpose of this pre-validation study was to determine if urinary PGE-M levels can be used as a biomarker to discriminate between healthy patients and those with colorectal disease. METHODS: Urine PGE-M was assessed in a total of 228 patients with CRC, colonic adenomatous polyps, Crohn's disease, and in subjects with no endoscopically detectable disease. Thirteen rectal carcinoma patients were treated with celecoxib and urinary PGE-M was measured before and after treatment. RESULTS: Urine PGE-M levels were increased among healthy men compared with healthy women (median, 8.59 [interquartile range (IQR), 5.67-22.3] vs 4.25 [IQR, 2.35-6.03], P = .0027). Urine PGE-M levels among patients with Crohn's disease (median, 19.85 [IQR, 6.89-90.2]), CRC (median, 14.65 [IQR, 5.94-92.1]), or large adenomas greater than 1 cm in size (median, 18.85 [IQR, 11.9-25.6]) were significantly increased when compared with patients who had either small polyps less than 1 cm in size (median, 9.69 [IQR, 6.41-22.2]), or no polyps (median, 7.05 [IQR, 2.35-24.7]) (P = .0001). PGE-M levels decreased significantly after celecoxib treatment in patients with rectal cancer (median, 21.7 [IQR, 16.2-29.9] vs 9.14 [IQR, 7.14-13.2], P = .009). CONCLUSIONS: The increase in urinary PGE-M in patients with colorectal cancers and large adenomas suggests that urinary PGE-M is a potentially useful biomarker for the detection of advanced colorectal neoplasia.     

Transjugular intrahepatic portosystemic shunt as a bridge to non-hepatic surgery in cirrhotic patients with severe portal hypertension: a systematic review

Background

Portal hypertension (PHTN) increases the risk of non-hepatic surgery in cirrhotic patients. This first systematic review analyzes the place of transjugular intrahepatic portosystemic shunt (TIPS) in preparation for non-hepatic surgery in such patients.

Real world perspective of coronary chronic total occlusion in third world countries: A tertiary care centre study from northern India

ObjectivesThe aim of this study is to determine the prevalence, clinical characteristics, angiographic profile and predictors of outcome for percutaneous coronary interventions (PCI) of coronary chronic total occlusions (CTO) in a tertiary referral centre of north India.BackgroundThere is no data on the prevalence and very few reports on clinical characteristics, angiographic profile and outcome of PCI in CTO from India.MethodsRetrospective analysis was done for the data of 12,020 patients undergoing coronary angiography (CAG) between January 2018 to January 2019 at our centre. Detailed baseline clinical, angiographic and revascularization data was collected. Outcome of CTO PCI was also noted. All baseline parameters were analysed for predicting the outcome of CTO PCI.ResultsCTO was identified in 16.3% (1968) patients undergoing CAG and in 24.4% of patients with hemodynamically significant CAD. CTO was predominantly found in LAD (48%) followed by RCA (42.9%) and LCx (25.3%) arterial distribution. Mean JCTO score was 1.93 ± 0.7. PCI as a management strategy was adopted in 456 of 1968 patients (23.1%) and was successful in 340 of 456 (74.6%) of patients. Almost all CTO PCI were attempted by an antegrade approach only. Increasing age, male sex, CTO in LCx arterial distribution and higher J CTO score were associated with poorer outcome in CTO PCI.ConclusionsCTO’s are commonly encountered during CAG procedures. In patients undergoing CTO PCI, a fair success rate can be achieved in a high volume experienced centre.