Preparation and Physical Characterization of DNA Binding Cationic Liposomes.

Cationic liposomes are routinely employed as one of the major nonviral transfecting agents for intracellular delivery of hydrophilic molecules such as nucleic acids, peptides, and proteins. Cationic liposomes when complexed with DNA form a strong positively charged cationic liposome-DNA complex or lipoplex. The chapter discusses, primarily, the major preparation technique for cationic liposomes and its physical characterization, with a focus on SYBR Green I dye exclusion assay and DNA encapsulation enhancement by freeze-thaw technique. SYBR Green I dye exclusion assay is a technique to determine the total amount of liposomal lipids required to bind a unit weight of DNA, which is critical for transfection experiments. Freeze-thaw technique on the other hand is one of the major techniques to improve DNA encapsulation efficiency in liposomes.

Shared Decision-Making and Medicolegal Aspects: Delivering High-Quality Cancer Care in India.

It is often difficult for people with cancer to make decisions for their care. The aim of this review is to understand the importance of shared decisionmaking (SDM) in Indian clinical scenario and identify the gaps when compared to practices in the Western world. A systematic search (2000-2019) was executed in Medline and Google Scholar using predefined keywords. Of the approximate 400 articles retrieved, 43 articles (Indian: 5; Western: 38) were selected for literature review. Literature review revealed the paucity of information on SDM in India compared to the Western world data. This may contribute to patientreported physical or psychological harms, life disruptions, or unnecessary financial costs. Western world data demonstrate the involvement and sharing of information by both patient and physician, collective efforts of the two to build consensus for preferred treatment. In India, involvement of patients in the planning for treatment is largely limited to tertiary care centers, academic institutes, or only when the cost of therapy is high. In addition, cultural beliefs and prejudices impact the extent of participation and engagement of a patient in disease management. Communication failures have been found to strongly correlate with the medicolegal malpractice litigations. Research is needed to explore ways to how to incorporate SDM into routine oncology practice. India has a high unmet need towards SDM in diagnosis and treatment of cancer. Physicians need to involve patients or their immediate family members in decision making, to make it a patient-centric approach as well. SDM enforces to avoid uninformed decisionmaking or a lack of trust in the treating physician's knowledge and skills. Physician and patient education, development of tools and guiding policies, widespread implementation, and periodic assessments may advance the practice of SDM.

Advanced Lipid Technologies® (ALT®): A Proven Formulation Platform to Enhance the Bioavailability of Lipophilic Compounds.

Despite recent advances, the drug development process continues to face significant challenges to efficiently improve the poor solubility of active pharmaceutical ingredients (API) in aqueous media or to improve the bioavailability of lipid-based formulations. The inherent high intra- and interindividual variability of absorption of oral lipophilic drug leads to inconsistent and unpredictable bioavailability and magnitude of the therapeutic effect. For this reason, the development of lipid-based drugs remains a challenging endeavour with a high risk of failure. Therefore, effective strategies to assure a predictable, consistent, and reproducible bioavailability and therapeutic effect for lipid-based medications are needed. Different solutions to address this problem have been broadly studied, including the approaches of particle size reduction, prodrugs, salt forms, cocrystals, solid amorphous forms, cyclodextrin clathrates, and lipid-based drug delivery systems such as self-emulsifying systems and liposomes. Here, we provide a brief description of the current strategies commonly employed to increase the bioavailability of lipophilic drugs and present Advanced Lipid Technologies® (ALT®), a combination of different surfactants that has been demonstrated to improve the absorption of omega-3 fatty acids under various physiological and pathological states.

Preparation and Physical Characterization of DNA-Binding Cationic Liposomes.

DNA-binding cationic liposomes are routinely employed as one of the major non-viral transfecting agents delivering DNA and other genes inside the cells. Cationic liposomes when complexed with DNA form a strong positively charged liposome-DNA complex or lipoplex. The chapter discusses primarily the major preparation technique for cationic liposomes and its physical characterization, with a focus on SYBR Green-I dye exclusion assay and DNA encapsulation enhancement by freeze-thaw technique. SYBR Green-I dye exclusion assay is a technique to determine the total amount of liposomal lipids required to bind a unit weight of DNA, which is critical for transfection experiments. Freeze-thaw technique on the other hand is one of the major techniques to improve DNA encapsulation in cationic liposomes.

Herbo-mineral supplementation in men with idiopathic oligoasthenoteratospermia : A double blind randomized placebo-controlled trial.

INTRODUCTION: There is insufficient scientific data on the medical management options for idiopathic oligoasthenoteratospermia (iOATs). We conducted a double blind, randomized, placebo-controlled trial to assess the efficacy and safety of the herbo-mineral supplement, Addyzoa(®), in infertile men with iOATs. We also evaluated its effect on semen reactive oxygen species (ROS) levels, total antioxidant capacity (TAC) and DNA fragmentation index. MATERIALS AND METHODS: Fifty infertile men with iOATS were recruited into an institutional ethics committee approved protocol from April to August 2009. Randomization was done using numbered, identical containers. Baseline semen samples were evaluated for routine parameters, ROS level, DNA fragmentation index and TAC. Drug/placebo was administered at a dose of two capsules twice a day for 3 months. All parameters were reassessed at 3 months and clinical side-effects were recorded. The study was registered with the Clinical Trials Registry of India and is available at www.ctri.in as study protocol number CTRI/2009/091/000551. RESULTS: Forty-four subjects completed the study, 21 in the drug arm and 23 in the placebo arm. There was no difference in baseline parameters between the two groups. Men in the drug group had significant improvement in mean total motility from 23.2 ± 17.3% to 33.4 ± 23.2% (P-value: 0.008) and mean progressive (Type A+B) motility from 15.7 ± 12.6% to 22.6 ± 18.0% (P-value: 0.024). ROS, TAC and DFI did not change significantly in either group and did not show any correlation with other semen parameters. CONCLUSIONS: Treatment with Addyzoa resulted in a significant improvement in total and progressive motility in the semen of men with iOATs after 3 months of therapy. There was no change in the sperm concentration, ROS, DFI or TAC levels.

Safety and efficacy of PCNL for management of staghorn calculi in pediatric patients.

OBJECTIVES: There are few reports on the use of PCNL for staghorn calculi in children. We evaluated the safety and efficacy of this technique, using adult equipment, in children below 16 years of age. METHODS: Data for pediatric patients undergoing PCNL for staghorn renal calculi was prospectively recorded. A staghorn calculus was defined as a branched stone occupying more than one part of the collecting system. A standard fluoroscopy guided PCNL was performed in the prone position using adult nephroscopes. Stone clearance was assessed on fluoroscopy and X-ray in all patients and an ultrasound or CT scan in selected cases. RESULTS: Beginning October 2007, 33 pediatric patients underwent 34 PCNLs at our center. 12 of these children had staghorn calculi. All patients had normal renal function and no metabolic abnormality. One child had a solitary kidney. In 5 children, the primary tract was placed into the superior calyx and 4 of these were above the 12th rib. A 21Fr nephroscope was used through a 24Fr tract in 9 children while a 26Fr nephroscope was used through a 30Fr tract in 3 cases. 10 children were managed through a single tract. One patient each required SWL and ureteroscopy for residual fragments. 11 patients had complete clearance while 1 had insignificant residue. One child required intravenous antibiotics for post-operative fever while another developed an abdominal collection that was managed conservatively. CONCLUSIONS: PCNL is safe and effective in the management of pediatric staghorn calculi.

Approaches for targeting mitochondria in cancer therapy.

The recognition of the role that mitochondria play in human health and disease is evidenced by the emergence in recent decades of a whole new field of "Mitochondrial Medicine". Molecules located on or inside mitochondria are considered prime pharmacological targets and a wide range of efforts are underway to exploit these targets to develop targeted therapies for various diseases including cancer. However the concept of targeting, while seemingly simple in theory, has multiple subtly different practical approaches. The focus of this article is to highlight these differences in the context of a discussion on the current status of various mitochondria-targeted approaches to cancer therapy.

Bilateral ureteric quadruplication with renal calculus.

Ureteric quadruplication is an extremely rare congenital anomaly. We present radiologic images of a young woman with a renal calculus with bilateral ureteric quadruplication. She presented with right flank pain, and the intravenous urogram revealed a calculus in the superior calyx that drained into the upper most moiety of a partially quadruplicated ureter.

Perforation of the gall bladder following typhoid fever-induced ileal perforation.

Gall bladder perforation is a potentially life-threatening condition. Spontaneous perforation is infrequent and rarely seen in the absence of gallstones but gall bladder perforation is an occasional complication of typhoid fever. If such perforations are not treated in time, mortality rates are very high. We report a case of gall bladder perforation complicating typhoid fever following enteric perforation of the ileum necessitating sequential laparotomies during the same admission.

Dorsal onlay buccal mucosal graft urethroplasty in long anterior urethral stricture.

OBJECTIVE: To assess the success of buccal mucosal graft (BMG) urethroplasty by the dorsal onlay technique in long anterior urethral stricture (> 2 cm long) through the midline perineal incision. MATERIALS AND METHODS: From January 1998 to December 2003, 43 patients with long anterior urethral strictures were managed by dorsal onlay BMG urethroplasty. After voiding trial, they were followed up at 3 months with uroflowmetry, retrograde urethrogram (RGU) and American Urological Association symptoms score (AUA symptoms scores). Successful outcome was defined as normal voiding with a maximum one attempt of visual internal urethrotomy (VIU) after catheter removal. Patients were further followed-up with uroflowmetry at 3 months interval and RGU every 6 months interval. RESULTS: Mean stricture length was 4.8 cm (range 3 to 9 cm) and mean follow up was 48 months (range 12 to 84 months). Only five patients were found to develop stricture at anastomotic site, during follow-up. Two of them voided normally after single attempt of VIU. Other three patients (6.9%) required further open surgery or repeat VIU during follow up and were considered as failure. CONCLUSION: Dorsal onlay BMG urethroplasty is a simple technique with good surgical outcome.

Dorsal onlay buccal mucosal graft urethroplasty in long anterior urethral stricture

OBJECTIVE: To assess the success of buccal mucosal graft (BMG) urethroplasty by the dorsal onlay technique in long anterior urethral stricture (> 2 cm long) through the midline perineal incision. MATERIALS AND METHODS: From January 1998 to December 2003, 43 patients with long anterior urethral strictures were managed by dorsal onlay BMG urethroplasty. After voiding trial, they were followed up at 3 months with uroflowmetry, retrograde urethrogram (RGU) and American Urological Association symptoms score (AUA symptoms scores). Successful outcome was defined as normal voiding with a maximum one attempt of VIU after catheter removal. Patients were further followed-up with uroflowmetry at 3 months interval and RGU every 6 months interval. RESULTS: Mean stricture length was 4.8 cm (range 3 to 9 cm) and mean follow up was 48 months (range 12 to 84 months). Only five patients were found to develop stricture at anastomotic site, during follow-up. Two of them voided normally after single attempt of VIU. Other three patients (6.9 percent) required further open surgery or repeat VIU during follow up and were considered as failure. CONCLUSION: Dorsal onlay BMG urethroplasty is a simple technique with good surgical outcome.

Xanthogranulomatous pyelonephritis: our experience with review of published reports.

BACKGROUND: The aim of this study was to analyse the cases of xanthogranulomatous pyelonephritis with review of published reports. METHODS: We retrospectively reviewed all nephrectomy specimens during February 1995 to January 2006. We found 26 cases of xanthogranulomatous pyelonephritis. We prepared a chart of these cases consisting of preoperative symptoms, laboratory findings, radiological imaging results and preoperative diagnosis. Open nephrectomy was carried out in all cases. RESULTS: Age group of the patients was 6-65 years and male : female ratio was 1.6:1. Twenty-two patients presented to us with intermittent high-grade fever, 21 with flank pain, 18 with loin mass, 2 with haematuria and 1 was detected during screening of vague gastrointestinal symptoms. Twenty-five patients had pyuria and only 10 had sterile urine culture. In all patients, only one kidney was affected. All patients had renal calculi 10-42 mm in size with bilaterally enlarged kidneys. Ipsilateral kidney was enlarged because of hydronephrosis or pyonephrosis in all cases and contralateral kidney was enlarged because of compensatory hypertrophy in 13 cases. Ipsilateral kidney had severely compromised renal function in all cases. Associated psoas abscess was present in one and tuberculosis in another. CONCLUSION: Xanthogranulomatous pyelonephritis is a relatively rare entity that is associated with obstruction, stones and infection of the urinary tract. Late presentation leads to loss of renal parenchyma. It cannot be differentiated preoperatively with renal tumours (renal cell carcinoma and Wilms' tumour), pyonephrosis, infected hydronephrosis and renal lymphoma. Nephrectomy and antibiotics are the treatment of choice.