Effect of preoperative biliary drainage on outcome of classical pancreaticoduodenectomy

AIM: To investigate the role of preoperative biliary drainage (PBD) in the outcome of classical pancreaticodu odenectomy. METHODS: A 10-year retrospective data analysis was performed on patients (n = 48) undergoing pancreaticoduodenectomy from March 1994 to March 2004 in department of surgery at SMS medical college, Jaipur, India. Demographic variables, details of preoperative stenting, operative procedure and post operative complications were noted. RESULTS: Preoperative biliary drainage was performed in 21 patients (43.5%). The incidence of septic complications was significantly higher in patients with biliary stent placement (P < 0.05, 0 vs 4). This group of patients also had a significantly higher minor biliary leak rate. Mortality and hospital stay in each group was comparable. CONCLUSION: Within this study population the use of PBD by endoscopic stenting was associated with a high incidence of infective complications. These findings do not support the routine use of biliary stenting in patients prior to pancreatico-duodenectomy.     

Mechanisms of inhibited liver tissue repair in toxicant challenged type 2 diabetic rats

Liver injury initiated by non-lethal doses of CCl(4) and thioacetamide (TA) progresses to hepatic failure and death of type 2 diabetic (DB) rats due to failed advance of liver cells from G(0)/G(1) to S-phase and inhibited tissue repair. Objective of the present study was to investigate cellular signaling mechanisms of failed cell division in DB rats upon hepatotoxicant challenge. In CCl(4)-treated non-diabetic (non-DB) rats, increased IL-6 levels, sustained activation of extracellular regulated kinases 1/2 (ERK1/2) MAPK, and sustained phosphorylation of retinoblastoma protein (p-pRB) via cyclin D1/cyclin-dependent kinase (cdk) 4 and cyclin D1/cdk6 complexes stimulated G(0)/G(1) to S-phase transition of liver cells. In contrast to the non-DB rats, CCl(4) administration led to lower plasma IL-6, decreased ERK1/2 activation, lower cyclin D1, and cdk 4/6 expression resulting in decreased p-pRB and inhibition of liver cell division in the DB rats. Furthermore, higher TGFbeta1 expression and p21 activation may also contribute to decreased p-pRB in DB rats compared to non-DB rats. Similarly, after TA administration to DB rats, down-regulation of cyclin D1 and p-pRB leads to markedly decreased advance of liver cells from G(0)/G(1) to S-phase and tissue repair compared to the non-DB rats. Hepatic ATP levels did not differ between the DB and non-DB rats obviating its role in failed tissue repair in the DB rats. In conclusion, decreased p-pRB may contribute to blocked advance of cells from G(0)/G(1) to S-phase and failed cell division in DB rats exposed to CCl(4) or TA, leading to progression of liver injury and hepatic failure.     

Thermal processing and characterization of 316LVM cardiovascular stent

In the current investigation, annealing was employed as a means to improve the mechanical performance of 316LVM coronary stents. Two different temperatures (1000 degrees C and 1150 degrees C) were explored for the thermal processing of the device. Acid pickling was done as a pre-annealing step to remove the debris and slag material attached to the stent after laser cutting. Post annealing operation involved the electrochemical polishing of the device which was also a parameter for assessment of the feasibility of the annealing process. Microstructural characterization, balloon expandability and tensile testing of the stents were performed to characterize the properties after thermal treatment. A fine grained austenitic structure with marked improvement in the % elongation (>40%) could be achieved after annealing the stents at 1000 degrees C. Balloon expandability tests of the stents annealed at 1000 degrees C indicated that the device was implantable.     

Concomitant noncontiguous level (thoracic &; lumbar) spinal stenosis

Presented here is a prospective study assessing the efficacy of decompression of concomitant noncontiguous level (thoracic & lumbar) stenosis in accordance with neurological findings, nerve root blocks, and myelographically proven disease. The objective was to determine the efficacy, clinical outcome, and functional recovery in patients undergoing simultaneous decompression. No previous study has focussed on the clinical outcome of such simultaneous decompression. Twenty-one patients with neurological claudication, progressive gait disturbance, upper motor neuron symptoms, and findings of myelopathy in both the lower extremities underwent simultaneous decompression and were assessed. The average follow-up was 32 months (range, 24-40 months). At the last examination,13 patients (82%) had excellent or good clinical results. Postoperative improvement correlated inversely with the duration of symptoms. The patients usually had satisfactory outcomes when the correct diagnosis was made and management was implemented. Functional recovery depends on early diagnosis and timely surgical intervention.     

Bioconjugation of polymers: a novel platform for targeted drug delivery

Bioconjugation, a novel technique is usually exploited to improve the biopharmaceutical aspects of a bioactive as well as afford its spatial and temporal distribution. The strategy enlightens newer vistas for delivery of drugs, peptides, enzymes, and oligonucleotides. Site specific delivery may be obtained by tailoring the conjugates as an inactive prodrug and designing polymer drug linkages susceptible to cleavage by specific enzymes or pH. These prodrugs substantially change the mechanisms of cellular entry, pharmacokinetic disposition and ultimately target the drug. The conjugate vehicles are being exploited for targeting pharmacological agents to visceral tissues viz brain, colon etc. These biomaterials are bringing into play, novel drug delivery systems for selectively and specifically ferrying drugs to the desired organ. Noteworthy contributions reported with bioconjugated nanoparticles for biosensing and bioimaging incorporate cell staining, DNA detection, separation and recombination relevance in DNA protection. Only recently, these tailor-made polymers have also gained impetuous for enzyme therapy, gene therapy, insulin therapy, cancer therapy and management of AIDS with the interception of minimal side effects. The present review exhaustively provides an insight to the polymer bioconjugates and their implications for targeted delivery. The article also discusses the therapeutic aspects of these conjugates and that these may serve as fascinating tools for drug delivery.     

Polyvalent dendrimer-methotrexate as a folate receptor-targeted cancer therapeutic

Our previous studies have demonstrated that a generation 5 dendrimer (G5) conjugated with both folic acid (FA) and methotrexate (MTX) has a higher chemotherapeutic index than MTX alone. Despite this, batch-to-batch inconsistencies in the number of FA and MTX molecules linked to each dendrimer led to conjugate batches with varying biological activity, especially when scaleup synthesis was attempted. Since the MTX is conjugated through an ester linkage, there were concerns that biological inconsistency could also result from serum esterase activity and differential bioavailability of the targeted conjugate. In order to resolve these problems, we undertook a novel approach to synthesize a polyvalent G5-MTX(n) conjugate through click chemistry, attaching the MTX to the dendrimer through an esterase-stable amide linkage. Surface plasmon resonance binding studies show that a G5-MTX(10) conjugate synthesized in this manner binds to the FA receptor (FR) through polyvalent interaction showing 4300-fold higher affinity than free MTX. The conjugate inhibits dihydrofolate reductase, and induces cytotoxicity in FR-expressing KB cells through FR-specific cellular internalization. Thus, the polyvalent MTX on the dendrimer serves the dual role as a targeting molecule as well as a chemotherapeutic drug. The newly synthesized G5-MTX(n) conjugate may serve as a FR-targeted chemotherapeutic with potential for cancer therapy.     

Achieving a Desired Esthetic Outcome for a Single‐Tooth Implant Restoration with Tissue Excess Using a Multidisciplinary Treatment Approach: A Clinical Report

Achieving ideal emergence profile and restoration contours for implant‐supported prostheses in the anterior esthetic zone is a prime requisite. In this report, the patient presented with decreased restoration space and unfavorable tissue contours for an implant restoration. Correction of space deficiency and reshaping of excess bone height and soft tissue were planned and executed carefully prior to definitive restoration of a maxillary anterior missing tooth with an implant‐retained prosthesis. Post‐treatment evaluation of the papillary levels and soft tissue profile helped in assessing maintenance of the restored emergence profile.     

Endothelial Cells in Co-culture Enhance Embryonic Stem Cell Differentiation to Pancreatic Progenitors and Insulin-Producing Cells through BMP Signaling

Endothelial cells (ECs) represent the major component of the embryonic pancreatic niche and play a key role in the differentiation of insulin-producing β cells in vivo. However, it is unknown if ECs promote such differentiation in vitro. We investigated whether interaction of ECs with mouse embryoid bodies (EBs) in culture promotes differentiation of pancreatic progenitors and insulin-producing cells and the mechanisms involved. We developed a co-culture system of mouse EBs and human microvascular ECs (HMECs). An increase in the expression of the pancreatic markers PDX-1, Ngn3, Nkx6.1, proinsulin, GLUT-2, and Ptf1a was observed at the interface between EBs and ECs (EB-EC). No expression of these markers was found at the periphery of EBs cultured without ECs or those co-cultured with mouse embryonic fibroblasts (MEFs). At EB-EC interface, proinsulin and Nkx6.1 positive cells co-expressed phospho-Smad1/5/8 (pSmad1/5/8). Therefore, EBs were treated with HMEC conditioned media (HMEC-CM) suspecting soluble factors involved in bone morphogenetic protein (BMP) pathway activation. Upregulation of PDX-1, Ngn3, Nkx6.1, insulin-1, insulin-2, amylin, SUR1, GKS, and amylase as well as down-regulation of SST were detected in treated EBs. In addition, higher expression of BMP-2/-4 and their receptor (BMPR1A) were also found in these EBs. Recombinant human BMP-2 (rhBMP-2) mimicked the effects of the HMEC-CM on EBs. Noggin (NOG), a BMP antagonist, partially inhibited these effects. These results indicate that the differentiation of EBs to pancreatic progenitors and insulin-producing cells can be enhanced by ECs in vitro and that BMP pathway activation is central to this process.