Diagnosis and management of aorto-left ventricular tunnel.

BACKGROUND: Aorto-left ventricular tunnel (ALVT) is a rare congenital extracardiac channel with progressive left ventricular dilatation needs early correction. MATERIALS AND METHODS: This is a report of diagnosis and management of aorto-left ventricular tunnel (ALVT) over a period of 11 years from a single institution. Seven patients (age range: 7 days-45 years) presented with heart failure. The diagnosis of ALVT was made by transthoracic echocardiogram in all cases. RESULTS: Treatment was refused by two patients who died during follow-up. Surgical closure of the tunnel was done in four cases, of which one needed Bentall procedure. Two patients had residual leak after the surgery. Transcatheter closure using Amplatzer muscular device was performed in two cases (for postoperative residual leak in one and primary procedure in the other). Significant hemolysis developed in one of them, necessitating the removal of the device and closed surgically. This child underwent aortic valve replacement two years later. All the remaining patients were doing well during the median follow-up of 30 months (range: 1.5-9 years). CONCLUSION: ALVT is a rare and potentially fatal anomaly that is ideally managed surgically. Catheter closure has a limited role.

Urinary tract infections-microbial virulence determinants and reactive oxygen species.

The human urinary tract is able to combat with the microbial invasion under normal circumstances. To cause urinary tract infection the organism has to evade the host defense mechanisms by possessing distinct properties which contribute to the virulence of the organism hence called virulence determinants Ninety percent of uncomplicated urinary tract infections are caused by Escherichia coli, hence the knowledge of the virulence determinants of this organism can be extrapolated to other uropathogenic organism as well. Virulence determinants of uropathogenic E. coli include adhesins, siderophore production, polysaccharide coating, hemolysin production, outer membrane proteins etc. The intestinal E. coli, which are the reservoir of E. coli for causing UTI, lack these virulence determinants. On the other hand these virulence determinants enable the organism to colonize and invade the urinary tract. In addition these are important in acquiring the nutrients in other wise nutrient deficient environment. Further, they also help the organisms in triggering an inflammatory response and hence bringing about pathological changes which leads to symptomatic UTI. Severity of symptomatic infections and tissue damage during the infective process depends upon the magnitude of the inflammatory response triggered by the uropathogen which in turn is dependent upon the amount of extrcellular release of reactive oxygen species by the phagocytic cells; hence role of antioxidants as an adjunct to antibiotics in the treatment of infective process needs to be evaluated further.

Prediction of cystine connectivity using SVM.

One of the major contributors to protein structures is the formation of disulphide bonds between selected pairs of cysteines at oxidized state. Prediction of such disulphide bridges from sequence is challenging given that the possible combination of cysteine pairs as the number of cysteines increases in a protein. Here, we describe a SVM (support vector machine) model for the prediction of cystine connectivity in a protein sequence with and without a priori knowledge on their bonding state. We make use of a new encoding scheme based on physico-chemical properties and statistical features (probability of occurrence of each amino acid residue in different secondary structure states along with PSI-blast profiles). We evaluate our method in SPX (an extended dataset of SP39 (swiss-prot 39) and SP41 (swiss-prot 41) with known disulphide information from PDB) dataset and compare our results with the recursive neural network model described for the same dataset.

Protein kinase Cs and tyrosine kinases in permissive action of prostacyclin on cerebrovascular regulation in newborn pigs.

The involvement of protein kinase C (PKC) and protein tyrosine kinase (PTK) in hypercapnia-induced cerebral vasodilation in newborn pigs was investigated with closed cranial windows using the PKC stimulator phorbol 12-myristate 13-acetate (PMA), and the PTK inhibitors, genistein and herbimycin A. The influence of prostaglandin I2 was eliminated using the prostaglandin cyclooxygenase inhibitor, indomethacin. Changes in pial arteriolar diameters in response to hypercapnia [partial pressure of arterial CO2 approximately 9.3 kPa (70 torr)] were analyzed. Genistein (40 micrograms/mL), herbimycin A (10 microM), or PMA (1 microM) did not affect cerebral vasodilation to hypercapnia when applied topically. Indomethacin (5 mg/kg i.v.) treatment blocked the dilation to hypercapnia and attenuated hypercapnia-induced increase in cortical cAMP. Genistein and herbimycin A restored the response to hypercapnia to indomethacin-treated piglets. PMA also restored the pial arteriolar dilation and the cAMP response to hypercapnia to indomethacin-treated piglets. One-hour exposure to 10 microM PMA, to down-regulate PKC, blocked vasodilation to hypercapnia but did not inhibit vasodilation to sodium nitroprusside. After prolonged (2 h) topical exposure of indomethacin-treated piglets to 10 microM PMA, neither genistein nor iloprost could restore dilation to hypercapnia. These results indicate that PKC stimulation and/or PTK inhibition may permit hypercapnia-induced vasodilation. These data further suggest that PKC is downstream from PTK in the regulatory pathway. Because previous data showed prostaglandin I2 at subdilator concentrations can also return dilation to hypercapnia to piglets treated with indomethacin, prostaglandin I2 could provide its permissive input by activating PKC and/or inhibiting PTK.