Recent Advancements in the Treatment of Alzheimer's Disease: A Multitarget-directed Ligand Approach.

Alzheimer's disease (AD) is a neurodegenerative disease and one of the leading causes of progressive dementia, affecting 50 million people worldwide. Many pathogenic processes, including amyloid ß aggregation, tau hyperphosphorylation, oxidative stress, neuronal death, and deterioration of the function of cholinergic neurons, are associated with its progression. The one-compound-one-target treatment paradigm was unsuccessful in treating AD due to the multifaceted nature of Alzheimer's disease. The recent development of multitarget-directed ligand research has been explored to target the complementary pathways associated with the disease. We aimed to find the key role and progress of MTDLs in treating AD; thus, we searched for the past ten years of literature on "Pub- Med", "ScienceDirect", "ACS" and "Bentham Science" using the keywords neurodegenerative diseases, Alzheimer's disease, and multitarget-directed ligands. The literature was further filtered based on the quality of work and relevance to AD. Thus, this review highlights the current advancement and advantages of multitarget-directed ligands over traditional single-targeted drugs and recent progress in their development to treat AD.

Tubeless percutaneous nephrolithotomy in patients with previous ipsilateral open renal surgery: a feasibility study with review of literature.

PURPOSE: To present our initial experience of tubeless percutaneous nephrolithotomy (PCNL) in patients with previous ipsilateral open renal surgery. PATIENTS AND METHODS: Twenty-five patients with previous ipsilateral open renal surgery underwent tubeless PCNL at our institute. Patients with large renal and/or upper ureteral calculi, irrespective of the number and size of the stones, amount of hydronephrosis, or the renal parameters, were selected for the procedure. Exclusion criteria were patients needing more than two percutaneous tracts, significant bleeding, and a significant residual stone burden that would necessitate a staged PCNL. The perioperative outcome of these patients (study group) was retrospectively compared with an historic cohort of the same number of patients with a history of open surgery for renal calculi who underwent ipsilateral PCNL with routine placement of a nephrostomy tube (control group). RESULTS: The two groups had comparable demographic data. Patients in the study group needed less postoperative analgesia (P = 0.000). They were discharged a mean of 10 hours earlier (P = 0.000). Two patients in both groups required blood transfusion. No urinoma or urinary leak from the nephrostomy site occurred in the study group. The incidence of other postoperative complications was comparable in both groups. Complete stone clearance was achieved in 88% of patients in the study group and 84% patients in the control group. CONCLUSION: The tubeless approach in patients with a history of open renal surgery is associated with decreased analgesia requirement and hospital stay without compromising stone-free rates or increasing the complications.

Splenic injury: rare complication of percutaneous nephrolithotomy: report of two cases with review of literature.

BACKGROUND: Splenic injury is an uncommon complication of percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We report herewith two cases of splenic injury that occurred during puncture of the 10th intercostal-space for PCNL. RESULTS AND CONCLUSIONS: One of these patients presented with hypotension on day 5 after discharge from the hospital. Both patients needed emergency laparotomy, and one of them required splenectomy for management of the injury. We reviewed the literature to determine the risk factors and management of splenic injury during PCNL.

Peri-operative complications of holmium laser enucleation of the prostate: experience in the first 280 patients, and a review of literature.

OBJECTIVE: To evaluate, in a prospective study, the complications in 280 patients undergoing holmium laser enucleation of the prostate (HoLEP) at our institution, and to review previous reports to determine the overall incidence and types of various complications, and analyse their causes and means of prevention. PATIENTS AND METHODS: We analysed the patients' demographic, peri-operative and follow-up data, and the complications during and after surgery. RESULTS: HoLEP was completed successfully in 268 patients (95.7%); eight required conversion to transurethral resection of the prostate (TURP) during the initial experience. The morcellation device and laser malfunctioned in two patients each. A blood transfusion was required during HoLEP in one patient; other complications included capsular perforation (9.6%), superficial bladder mucosal injury (3.9%) and ureteric orifice injury (2.1%). A blood transfusion was needed after HoLEP in 1.4% of patients and cystoscopy with clot evacuation in 0.7%. Transient urinary incontinence was the commonest complication after HoLEP, in 10.7% of patients, but recovered spontaneously in all except two (0.7%). Other rare complications were re-catheterization (3.9%), urinary tract infection (3.2%), epididymitis (0.7%), meatal and submeatal stenosis (2.5%), bulbar urethral stricture (2.1%), bladder neck contracture (0.35%) and myocardial infarction (0.35%). CONCLUSIONS: There was a low incidence of complications with HoLEP; most were minor and easily managed. Our results are comparable with those published previously, and establish HoLEP as safe and reproducible procedure. While gaining experience, HoLEP can be converted to TURP with no harm to the patient.

Prospective evaluation of the learning curve for holmium laser enucleation of the prostate.

PURPOSE: In a prospective manner we evaluated the learning experience of an endourologist inexperienced with holmium laser prostate enucleation and its impact on surgical outcome. We also reviewed the literature to document technical features of holmium laser prostate enucleation at different institutions. MATERIALS AND METHODS: Patient demographic, perioperative and followup data were analyzed. To assess the impact of the learning curve on postoperative outcome patients were divided into group 1--patients 1 to 50, group 2--51 to 100 and group 3--101 to 162. The effect of the learning curve and weight of resected tissue on enucleation and morcellation efficiency was studied. RESULTS: Holmium laser prostate enucleation was successfully completed in 93.82% of patients. Eight patients required conversion to transurethral prostate resection. Enucleation and morcellation efficiency was 0.49 and 2.75 gm per minute, respectively. Enucleation efficiency attained a plateau after 50 cases. Postoperative outcome was compared in the 3 patient groups. There was a higher incidence of capsular perforation and stenotic urethral complications in group 1. In the literature a mean of 57.09% of tissue (range -9.6 to 81.9%) was retrieved after holmium laser prostate enucleation and mean efficiency was 0.52 gm per minute (range -0.11 to 1.09). Efficiency increased proportionally with resected prostate weight. CONCLUSIONS: An endourologist inexperienced with holmium laser prostate enucleation can perform the procedure with reasonable efficiency after about 50 cases with an outcome comparable to that of experts, as described in the literature. During the learning curve conversion to transurethral prostate resection can be done without any harm to the patient.

Simultaneous transurethral cystolithotripsy with holmium laser enucleation of the prostate: a prospective feasibility study and review of literature.

OBJECTIVE: To report experience with holmium laser enucleation of the prostate (HoLEP) simultaneously with transurethral holmium laser cystolithotripsy (HLC) for managing bladder outlet obstruction (BOO) and associated vesical calculi; we also review previously reported cases of managing vesical calculi and associated BOO. PATIENTS AND METHODS: The high-powered holmium laser is a very efficient multifunctional endourological instrument that effectively fragments calculi of all compositions and is capable of haemostatic cutting of tissue, resulting in minimal bleeding after prostatic resection. A prospective study was conducted from April 2003 that included 32 men who underwent simultaneous HoLEP with transurethral HLC at our institution. Demographic, laboratory, peri-operative and follow-up data were analysed. Complications during and after surgery were identified to assess the morbidity of procedure. RESULTS: The mean (range) size of bladder calculi was 34.6 (12-70) mm and the preoperative weight of the prostate was 51.9 (11-172) g. Combined HoLEP with transurethral HLC was technically feasible in all patients, and all were stone-free after surgery. The mean operative duration was 97.7 (40-230) min, the weight of prostate tissue removed 34.6 (5-88) g, and the duration of catheterization and hospital stay 29.3 h and 34.8 h, respectively. Complications during and after surgery occurred in 12.5% and 15.6% of patients, respectively; all complication were minor and none caused any residual disability to the patient. No patient required a blood transfusion or developed clot retention. CONCLUSIONS: Managing bladder stones and BOO with simultaneous transurethral HLC and HoLEP should be considered the treatment of choice for such cases. Stones of any size and composition, and prostates of practically any size can be treated endoscopically using the holmium laser, with acceptable morbidity once the technique is mastered. The review of previous reports suggested a need for a prospective study comparing endoscopic management of BOO and associated bladder stones, with medical management of BOO and extracorporeal shock wave lithotripsy/endoscopic lithotripsy for bladder stone.