Effect of Probiotic Microbial Cell Preparation (MCP) on Fasting Blood Glucose, Body Weight, Waist Circumference, and Faecal Short Chain Fatty Acids among Overweight Malaysian Adults: A Pilot Randomised Controlled Trial of 4 Weeks

Introduction: Probiotic microbial cell preparation (MCP) supplementation is one of the approaches to modulate alterations in gut microbiota (GM). This double-blind randomised controlled trial investigated the effect of 4 weeks of MCP supplementation on fasting blood glucose levels (FBG), body weight (BW), waist circumference (WC), and faecal short chain fatty acids (SCFA) among 24 healthy and overweight (with BMI = 23 kg/m2) Malaysian adults. Methods: Twenty-six subjects were randomised to receive either MCP (n= 12) or placebo (n=14), twice daily, for 4 weeks. The probiotic powder contained a mix of six strains namely, Lactobacillus acidophilus, Lactobacillus lactis, Lactobacillus casei,Bifidobacterium longum, Bifidobacterium bifidum and Bifidobacterium infantis (3.0 x 1010 cfu). FBG, BW, WC, WHR, faecal SCFA, physical activity levels and dietary intake were measured and changes were determined using repeated measures ANOVA. Results: Twenty-four subjects successfully completed the 4-week study period. Changes in FBG, BW, WC and SCFA were not significantly different between the groups. Only subjects in the MCP group significantly reduced their energy intake compared to baseline (1671?±476 vs 1386?±447 kcal, P=0.045). Conclusion: A 4-week supplementation of the MCP mix powder did not have significant effects on the variables studied. However, the significant reduction in dietary energy intake in the MCP group suggests the potential of probiotics as an adjuvant to dietary therapy for weight los

AMPK activation regulates neuronal structure in developing hippocampal neurons.

AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a cellular and whole organism energy sensor to regulate ATP-consuming (anabolic) and ATP-generating (catabolic) pathways. The heterotrimeric AMPK complex consists of a catalytic α-subunit, regulatory ß-subunit, and an AMP/ATP-binding γ-subunit. Several alternate isoforms exist for each subunit (α1, α2, ß1, ß2, γ1, γ2 and γ3). However, little is known of the expression pattern or function of the individual catalytic complexes in regulating neuronal structure. In this study, we examined the role of AMPK subunits in differentiating hippocampal neurons. We found that during development, the expression of AMPK subunits increase and that activation of AMPK by energetic stress inhibits neuronal development at multiple stages, not only during axon outgrowth, but also during dendrite growth and arborization. The presence of a single functional AMPK catalytic complex was sufficient to mediate these inhibitory effects of energetic stress. Activation of AMPK mediates these effects by suppressing both the mTOR and Akt signaling pathways. These findings demonstrate that the energy-sensing AMPK pathway regulates neuronal structure in distinct regions of developing neurons at multiple stages of development.

Assessment of antibiofilm activity of magnesium fluoride nanoparticles-stabilized oil-in-water nanosized emulsion.

CONTEXT: Magnesium fluoride (MgF(2)) nanoparticles-stabilized oil-in-water nanosized emulsion was prepared and assessed for its antiadherent and antibiofilm activities over glass coupons against pathogenic microorganisms like Escherichia coli and Staphylococcus aureus. OBJECTIVE: The major objectives of this paper are to synthesis MgF(2) nanoparticles, to prepare MgF(2) nanoparticles-stabilized nanosized emulsion, to coat glass coupons with MgF(2) nanoparticles and nanoparticles-stabilized emulsion, to challenge the emulsion or nanoparticles-coated and uncoated glass surfaces with fresh bacterial cultures over 18 h for biofilm formation, and to evaluate the extended antibiofilm activity of the coupons coated with either nanoparticles or emulsion in restricting the bacterial growth and biofilm formation. RESULTS AND DISCUSSION: Uncoated surfaces supported a massive biofilm formation (12.6 × 10(11) and 11.6 × 10(11) CFU cm(-2) for E. coli and S. aureus respectively for the 3rd day) while emulsion-coated surfaces dramatically restricted bacterial colonization (9.3 and 8.0 CFU cm(-2) for E. coli and S. aureus respectively). These results suggested that MgF(2) nanoparticles-stabilized emulsion is effective in restraining bacterial colonization on glass surfaces. CONCLUSION: Although the glass coupons are selected as a model biomaterial surface, similar or increased antibiofilm action would be expected when this 'hybrid' nanoparticulate system is coated on other types of biomaterial surfaces such as intraocular lenses, catheters, etc.

Normal mitral cell dendritic development in the setting of Mecp2 mutation.

Rett syndrome (RTT) is an autism spectrum disorder caused by mutation in the gene encoding methyl CpG binding protein 2 (MECP2). Evidence to date suggests that these disorders display defects in synaptic organization and plasticity. A hallmark of the pathology in RTT has been identified as decreased dendritic arborization, which has been interpreted to represent abnormal dendritic formation and pruning during development. Our previous studies revealed that olfactory axons display defective pathfinding and targeting in the setting of Mecp2 mutation. In the present work, we use Mecp2 mutant mouse models and the olfactory system to investigate dendritic development. Here, we demonstrate that mitral cell dendritic development proceeds normally in mutant mice, resulting in typical dendritic morphology at early postnatal ages. We also failed to detect abnormalities in dendritic inputs at symptomatic stages when glomeruli from mutant mice appear smaller in area than the wild type (WT) (6 weeks postnatally). Collectively, these findings suggest that the initial defects in glomeruli impairment seen with Mecp2 mutation do not result from abnormal dendritic development. Our results using the olfactory system indicate that dendritic abnormalities are not an early feature in the abnormalities incurred by Mecp2 mutation.

Percutaneous coronary intervention for persistent complete heart block complicating inferior myocardial infarction.

Current guidelines recommend implantation of permanent pacemakers for advanced atrioventricular block complicating acute myocardial infarction (MI) when the block is present beyond the usual hospital course. In patients with inferior MI, such blocks are usually transient, but they can also be persistent. However, they are not considered as primary indications for early reperfusion by percutaneous coronary intervention (PCI) in the absence of ongoing ischemia. We describe a patient with inferior MI in whom a successful PCI was effective in reversing persistent complete heart block, thus avoiding implantation of a permanent pacemaker. In selected patients with inferior MI and advanced atrioventricular block, PCI should be considered as a treatment option before recommending permanent pacemaker implantation.

Clinical Evaluation of an Indigenous Paclitaxel-Eluting Stent in De NovoCoronary Artery Stenosis.

BACKGROUND, Drug-eluting stents have enabled considerable reduction in restenosis in patients subjected to angioplasty. However, in view of high cost of drug-eluting stents, efforts to develop medicated stents at reduced cost using alternative polymers in Indian setting are imperative. Hence a multi-center study was undertaken to evaluate the safety and efficacy of the indigenously developed paclitaxel-eluting RELEASE-T stent. METHODS, The study included 100 patients (male:86, Female:14) who were undergoing angioplasty for various indications at four centres viz. Delhi, Hyderabad, Pune and Warangal. The age range was 29 - 76 years; 37 patients were diabetic. All patients were pre-treated with aspirin 150-325 mg plus clopidogrel 75 mg daily four days before procedure or clopidogrel alone. Aspirin was continued indefinitely. RESULTS, Direct stenting ws done in majority of patients. One patient, in whom stent could not be delivered, received only baloon angioplasty. Sixty-four patients had stenting of left anterior descending artery. The stent diameter ranged from 2.5 to 3.5 mm, and the length, 15 to 20 mm. All patients were followed up at 1,3 and 6 months. There was two deaths: one had subacute thrombosis on both stents, and the other (who was HIV positive) had sudden cardiac death. The 6-month rate of major adverse cardiac events was 4% and target lesion revascularization rate ws 2%. CONCLUSION, This ulti-locational study brings out that the use of indigenously developed paclitaxel-eluting stent is safe and clinically efficacious.

Sulfatides: targets for anti-phospholipid antibodies.

BACKGROUND: Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. Beta2-glycoprotein I is an anionic phospholipid-binding plasma protein, and the phospholipid-bound form is the target for most anti-phospholipid antibodies that are associated with recurrent thrombosis, miscarriages, and neurological symptoms. In this study, we examined whether beta2-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies. METHODS AND RESULTS: Beta2-glycoprotein I binds to surface-bound sulfatides but not to other glycolipids, such as ceramide, cerebrosides, sphingomyelin, or ganglioside. At a sulfatide coating density of 1 microg/well, beta2-glycoprotein I reaches half-maximal binding at 2.5 microg/mL, and the binding is saturated at 10 microg/mL. The binding of beta2-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant beta2-glycoprotein I concentration of 5 microg/mL, maximal binding of beta2-glycoprotein I is observed at a coating density of 1 mug/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound beta2-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-beta2-glycoprotein I complex by >50% in 12 of 14 patients. Furthermore, immunoaffinity-purified anti-cardiolipin antibodies from 4 of 5 patients reacted with sulfatide-bound beta2-glycoprotein I. CONCLUSIONS: These results show that not only anionic phospholipids, as commonly known, but also sulfatides are targets for most anti-phospholipid antibodies. We therefore postulate that interactions of these antibodies with sulfatides may contribute to some of the clinical symptoms of the anti-phospholipid antibody syndrome.

Risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter.

AIMS: Catheter ablation of the inferior vena cava-tricuspid annulus isthmus and continuation of antiarrhythmic drug therapy have been shown to be an effective hybrid therapy for atrial flutter which results from antiarrhythmic drug treatment of atrial fibrillation. The aim of this study was to determine the risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter. METHODS AND RESULTS: 90 patients with paroxysmal (n=46) or persistent atrial fibrillation (n=44) developed atrial flutter due to the administration of amiodarone (n=48), flecainide (n=22), propafenone (n=14) or sotalol (n=6). Recurrence of atrial fibrillation after ablation was assessed during follow-up on continued antiarrhythmic drug therapy and during long-term follow-up, irrespective of the initial antiarrhythmic medication. During the follow-up on continued antiarrhythmic drug therapy (16+/-13 months), recurrence of atrial fibrillation was documented in 24 of 90 patients (27%). The presence of accompanying pre-ablation episodes of atrial fibrillation on antiarrhythmic treatment (Odds ratio 7.1, 95% confidence interval 2.3 to 25, p=0.001) and decreased left ventricular ejection fraction (Odds ratio 3.7, 95% confidence interval 1.01 to 12.5, p=0.048) were significant and independent predictors of post-ablation atrial fibrillation. Antiarrhythmic medication was discontinued during long-term follow-up due to adverse drug effects (amiodarone, n=12; flecainide, n=1) in 13 patients (14%). During the long-term follow-up, irrespective of the initial antiarrhythmic medication (21+/-15 months), stable sinus rhythm was maintained in 60 of 90 patients (67%). CONCLUSION Hybrid therapy can be considered as the first line therapy for patients with antiarrhythmic drug-induced atrial flutter but patients should be carefully evaluated for accompanying pre-ablation episodes of atrial fibrillation and possible adverse drug effects before initiation of hybrid therapy.

Extensive dissection requiring multiple stents following balloon angioplasty for non-specific aorto-arteritis.

Discrete stenoses of the thoraco-abdominal aorta in non-specific aorto-arteritis are considered favorable lesions for balloon angioplasty characterized by good results without major complications. Herein, we describe one such case manifesting with severe hypertension, left ventricular dysfunction and congestive heart failure treated by angioplasty. Balloon dilatation, however, resulted in extensive dissection requiring implantation of two Wallstents. Over a follow-up of one year, hypertension remained under good control with fewer drugs and symptom relief was maintained. Left ventricular ejection fraction improved from 35% to 61%.

Successful inoue balloon valvotomy in a difficult case of mitral stenosis using multiple modifications of technique: alternative method for loop formation of the Inoue balloon catheter.

Transseptal puncture was accomplished with difficulty at an unfavorable site in a case of severe mitral stenosis with distorted atrial and septal anatomy. Septal balloon entrapment could not be avoided during attempts to cross the mitral valve using the standard technique. This problem was circumvented by resorting to the loop method and the left ventricle was entered first with a guidewire, which then supported the balloon catheter. Successful mitral valve dilatation could thus be performed. A simple alternative method that was used to form the Inoue balloon catheter into a loop is also described.

Percutaneous transseptal mitral commissurotomy in pregnant women with critical mitral stenosis.

BACKGROUND: Percutaneous transseptal mitral commissurotomy has been successfully performed in selected pregnant patients with severe symptomatic mitral stenosis. Its safety and efficacy needs to be evaluated in a large number of cases. METHODS AND RESULTS: Percutaneous transseptal mitral commissurotomy was performed in 85 severely symptomatic (New York Heart Association functional class III or IV) pregnant women aged 22.7+/-4.1 years (range 18-39 years) with critical mitral stenosis at 24.8+/-4.7 weeks (range 20-34 weeks) of gestation. Percutaneous valvotomy was performed using a flow-guided Inoue balloon in all the patients. The procedure was considered successful in 80 (94%) patients. The hemodynamic mean end-diastolic gradient decreased from 26.7+/-6.8 mm Hg (range 16-35 mmHg) to 4.5+/-3.8 mmHg (range 0-14 mmHg) (p<0.001). The mean diastolic gradient decreased from 29.1+/-9.1 mmHg (range 18-38 mmHg) to 7.2+/-4.1 mmHg (range 4.1-18 mmHg) (p<0.001). The mean mitral valve area assessed by echocardiography increased from 0.75+/-0.5 cm2 (range 0.4-1.0 cm2) to 2.0+/-0.5 (range 1.0-2.7 cm2) (p<0.001). The mean fluoroscopy time was 3.6+/-3.2 minutes. The results of the mitral valvotomy were considered suboptimal in 4 patients. Mitral regurgitation increased by 1 grade in 16 patients and more than 2 grades in 2 patients. One patient developed pericardial tamponade during the procedure and was managed by catheter drainage. Percutaneous mitral valve dilatation was then successfully performed in this patient. No fetal abortion occurred after the procedure. CONCLUSIONS: The results of this study indicate that percutaneous transseptal mitral commissurotomy is a safe and effective procedure for severe symptomatic mitral stenosis in pregnancy.

Vibrio cholerae O139 in Calcutta, 1992-1998: incidence, antibiograms, and genotypes.

We report results of surveillance for cholera caused by Vibrio cholerae O139 from September 1992, when it was first identified, to December 1998. V. cholerae O139 dominated as the causative agent of cholera in Calcutta during 1992-93 and 1996- 97, while the O1 strains dominated during the rest of the period. Dramatic shifts in patterns of resistance to cotrimoxazole, neomycin, and streptomycin were observed. Molecular epidemiologic studies showed clonal diversity among the O139 strains and continuous emergence of new epidemic clones, reflected by changes in the structure, organization, and location of the CTX prophages in the V. cholerae O139

Reduced rearing temperature augments responses in sympathetic outflow to brown adipose tissue.

Sympathetic outflow to brown adipose tissue (BAT) contributes to both thermoregulation and energy expenditure in rats through regulation of BAT thermogenesis. Acute cold exposure in mature animals augments BAT thermogenesis; however, the enhanced BAT thermogenic response returns to normal shortly after cessation of the cold exposure. In this study, we sought to determine whether cold exposure in early neonatal life could induce enhanced responses in the sympathetic outflow to BAT and whether this altered sympathetic regulation would be sustained after the cold stimulus was removed. BAT sympathetic nerve activity (SNA) was recorded in urethane-chloralose-anesthetized, artificially ventilated rats that were raised from birth in either 18 or 30 degrees C environments and then, at 8 weeks of age, were maintained in 23 degrees C for at least 4 weeks. An acute hypothermic stimulus, disinhibition of a brainstem thermogenic network in the raphe pallidus, or electrical stimulation in this raphe site produced increases in BAT SNA that were twice as great in rats reared at 18 degrees C as in those reared at 30 degrees C. The norepinephrine content of the interscapular BAT (IBAT) and the number of sympathetic ganglion cells projecting to interscapular BAT were 70% greater in the 18 degrees C-reared rats. We conclude that neonatal exposure to a cold environment induces a permanent developmental alteration in the capacity for sympathetic stimulation of BAT thermogenesis that may be mediated, in part, by a greater number of sympathetic ganglion cells innervating BAT in cold-reared animals.

Utility of coaxial technique for renal angioplasty in patients with a difficult-to-cross stenosis.

The aim of this study was to evaluate the feasibility of coaxial approach in difficult-to-cross lesions in patients with failed percutaneous transluminal renal angioplasty by conventional over-the-wire exchange technique. Twelve stenoses in 10 patients (six women and four men; age range 19 +/- 7 years) with uncontrolled hypertension were treated by this method. The stenosis was caused by nonspecific aortoarteritis in 8 patients and fibromuscular dysplasia in 2 patients. It was ostial in seven and post-ostial in five vessels. Conventional exchange technique was unsuccessful in all of them. All procedures were done by femoral route. Technical success was seen in 11 (92%), without complication. The stenosis improved from 90 +/- 2.1% (range 80-100%) to 6 +/- 7% (range 0-20%), blood pressure decreased from 198 +/- 12.3 mm Hg (range 180-220 mm Hg)/130 +/- 6.7 mm Hg (range 120-140 mm Hg) to 119 +/- 5.7 mm Hg (range 110-130 mm Hg)/83 +/- 3.9 mm Hg (range 80-90 mm Hg), and number of drug treatments for hypertension fell from 3.6 +/- 0.52 (range 3-4) to 1 +/- 0.94 (range 0-3; p < 0.01). Percutaneous transluminal renal angioplasty resulted in "cure" in 3 patients and "improvement" in 7 patients. Follow-up period was 3-21 months (mean 6.4 months). No restenosis was detected. Coaxial approach is safe and effective in treating difficult-to-cross lesions in which renal angioplasty by conventional exchange technique is unsuccessful.

Isolated congenital anterior mitral leaflet cleft: a rare cause of mitral insufficiency.

BACKGROUND AND AIM OF THE STUDY: Isolated cleft of the anterior mitral leaflet is a rare cause of mitral insufficiency. Although an established entity, due to its rarity the exact anatomic diagnosis is difficult to establish unless sought specifically. METHODS: Four patients (age range: 16 to 26 years) with isolated cleft of the anterior mitral leaflet were treated at the authors' institute. Clinical symptoms were typical of mitral insufficiency; the exact anatomic diagnosis was not established preoperatively in any patient. The cleft was directly sutured in all four patients and additional annuloplasty was performed in three. RESULTS: Postoperative echocardiography confirmed satisfactory results. After a mean follow up of 46.7 months (range: 3 to 84 months), one patient had mild mitral insufficiency and the remaining patients had no mitral regurgitation. CONCLUSION: In severe mitral insufficiency with no obvious mitral valve pathology and an intact atrial septum, a cleft of the anterior mitral leaflet should be sought. Repair of the cleft can restore normal mitral valve function.

Coarctation of Aorta Mimicking Aortic Arch Interruption and its Successful Dilatation by an Innovative Approach.

Balloon dilatation for coarctation of the aorta is an established alternative to surgery in older children and young adults with a high success rate and a low incidence of restenosis.1Ð4 However, balloon dilatation has to be performed with extreme caution when the coarct segment involves the major branches of the aortic arch or when the coarct has an atypical anatomy. Herein, we report an unusual case which was suggestive of aortic arch interruption on descending thoracic aortography and could not be crossed retrogradely. Brachial approach for ascending aortography revealed that this was indeed a coarct with a distorted anatomy and also made possible crossing of the coarct antegradely. After exteriorizing the guide wire across the coarct with the help of a snare device advanced through the femoral arterial sheath, the coarct could be dilated from the femoral route as is routinely done.