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Cancer often develops multidrug resistance (MDR) when cancer cells become resistant to numerous structurally and functionally different chemotherapeutic agents. MDR is considered one of the principal reasons for the failure of many forms of clinical chemotherapy. Several factors are involved in the development of MDR including increased expression of efflux transporters, the tumor microenvironment, changes in molecular targets and the activity of cancer stem cells. Recently, researchers have designed and developed a number of small molecule inhibitors and derivatives of natural compounds to overcome various mechanisms of clinical MDR. Unfortunately, most of the chemosensitizing approaches have failed in clinical trials due to non-specific interactions and adverse side effects at pharmacologically effective concentrations. Nanomedicine approaches provide an efficient drug delivery platform to overcome the limitations of conventional chemotherapy and improve therapeutic effectiveness. Multifunctional nanomaterials have been found to facilitate drug delivery by improving bioavailability and pharmacokinetics, enhancing the therapeutic efficacy of chemotherapeutic drugs to overcome MDR. In this review article, we discuss the major factors contributing to MDR and the limitations of existing chemotherapy- and nanocarrier-based drug delivery systems to overcome clinical MDR mechanisms. We critically review recent nanotechnology-based approaches to combat tumor heterogeneity, drug efflux mechanisms, DNA repair and apoptotic machineries to overcome clinical MDR. Recent successful therapies of this nature include liposomal nanoformulations, cRGDY-PEG-Cy5.5-Carbon dots and Cds/ZnS core–shell quantum dots that have been employed for the effective treatment of various cancer sub-types including small cell lung, head and neck and breast cancers. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection in renal allograft recipient is associated with increased morbidity and mortality. At present, only few studies related to treatment and outcomes of HCV-infected renal allograft recipients with DAAs have been published. We aimed the study to assess the efficacy and safety of sofosbuvir-based regimens in HCV-infected renal allograft recipients. We analyzed data of 22 eligible HCV-infected renal allograft recipients (14 genotype-3, 6 genotype-1, one each genotype-2 and 4) who were treated with DAAs at our institute. DAA regimen included sofosbuvir and ribavirin with or without ledipasvir or daclatasvir for 12--24 weeks. Patients were followed up for 24 weeks after completion of treatment. A rapid viral response of 91%, end of therapy response of 100%, and sustained viral response at 12 and 24 weeks of 100% with rapid normalization of liver enzymes were observed. Therapy was well tolerated except for ribavirin-related anemia. A significant decrease in tacrolimus trough levels was observed and most patients required increase in tacrolimus dose during the study. Treatment with newer DAAs is effective and safe for the treatment of HCV-infected renal allograft recipients. [ABSTRACT FROM AUTHOR]

Calcineurin inhibitors (CNIs) are the preferred drugs for treatment of childhood steroid-resistant nephrotic syndrome (SRNS) who are also resistant to cyclophosphamide (CYC). Although few studies have shown a benefit of one over the other, efficacy and safety of either CNIs (tacrolimus [TAC] or cyclosporine [CSA]) in this special population remained to be assessed in long-term studies. Forty-five children with SRNS who were also resistant to CYC (CYC-SRNS) from January 2006 to June 2011, were included in the study. Patients were treated with CNI either TAC or CSA based on 1:1 allocations and were prospectively observed. Patients who were nonresponsive to CNIs had been treated with mycophenolate mofetil. Outcomes were measured in terms of remission of NS, adverse effects of drugs, and progression of disease. After 6 months of treatment, 16/23 (69.5%) patients on CSA achieved remission and 18/22 (81.8%) on TAC achieved remission (P = 0.3). The side effects hypertrichosis, and gum hyperplasia were significantly less in TAC group as compared to CSA group (P < 0.001). The 1-, 2-, 3-, 4-, and 5-year estimated renal survival (doubling of serum creatinine as event) in CSA group was 96%, 91%, 85%, 54%, and 33% and in TAC group was 96%, 95%, 90%, 89%, and 79%, respectively (P = 0.02). Although TAC and CSA are equally efficacious, TAC has significantly less side effects. The long-term outcome of renal function was significantly better in patients who were treated with TAC as compared to CSA. [ABSTRACT FROM AUTHOR]

In renal allograft recipients, cytomegalovirus (CMV) typically causes tubulointerstitial nephritis. Only rarely glomeruli are involved. We present a rare case of CMV with collapsing glomerulopathy, necrotizing glomerulonephritis, and crescent formation in a renal allograft recipient. Immunohistochemistry confirmed CMV infection. The patient was started on valganciclovir and his renal function remained stable. A repeat renal biopsy performed three months later showed morphologically normal glomeruli and CMV immunostaining was also negative. Nephropathologists have to carefully screen for CMV in cases with crescentic or collapsing glomerulopathy as the later lesions resolve after treating the underlying viral infection. This study will add on to the various glomerular changes associated with CMV infection. [ABSTRACT FROM AUTHOR]

Cancer is a hyperproliferative disorder that involves transformation, dysregulation of apoptosis, proliferation, invasion, angiogenesis and metastasis. During the last 30 years, extensive research has revealed much about the biology of cancer. Chemotherapy and radiotherapy are the mainstays of cancer treatment, particularly for patients who do not respond to surgical resection. However, cancer treatment with drugs or radiation is seriously limited by chemoresistance and radioresistance. Various approaches and strategies are employed to overcome resistance to chemotherapy and radiation treatment. Many plant-derived phytochemicals have been investigated for their chemo- and radio-sensitizing properties. The peoples of South Asian countries such as India, Pakistan, Sri Lanka, Nepal, Bangladesh and Bhutan have a large number of medicinal plants from which they produce various pharmacologically potent secondary metabolites. The medicinal properties of these compounds have been extensively investigated and many of them have been found to sensitize cancer cells to chemo- and radio-therapy. This review focuses on the role of South Asian medicinal compounds in chemo- and radio-sensitizing properties in drug- and radio-resistant cancer cells. Also discussed is the role of South Asian medicinal plants in protecting normal cells from radiation, which may be useful during radiotherapy of tumors to spare surrounding normal cells. [ABSTRACT FROM AUTHOR]

Background Radiofrequency-induced heat therapy (RFHT) has been found to be safe and effective against cutaneous leishmaniasis (CL) in the short term, but its long-term efficacy is unclear. Objectives To compare the long-term efficacy of RFHT vs. intralesional sodium stibogluconate (SSG) injections in the treatment of CL in India. Methods One hundred patients with a confirmed diagnosis of CL were randomly assigned in a 1 : 1 ratio to receive topical RFHT for 30-60 s or seven intralesional injections of SSG (50 mg cm−2 of lesion). Improvement and recurrence were monitored every 15 days after the initiation of treatment for 4 months and then at 5, 6, 9, 12 and 18 months post-treatment; the rates of complete cure were compared. Results Lesions were healed in 47 out of 50 patients (94%) in the RFHT group and in 46 out of 50 patients (92%) in the SSG group at week 12. Time to complete healing was comparable in the two groups. At 6 months post-treatment, cure rates in the RFHT and SSG groups were 98% [95% confidence interval (CI) 94-100%] and 94% (95% CI 86-100%), respectively. Age, sex and lesion size or number had no effect on cure rates. No relapse of infection was recorded in cured patients in either group up to 12-18 months after initiation of treatment. Skin biopsies of cured lesions in eight out of eight (100%) patients from the RFHT group and three of three from the SSG group at 12 months showed minimal fibrosis and were negative for Leishmania tropica by polymerase chain reaction test. Conclusions A single application of RFHT is safe, cosmetically acceptable and effective in inducing a long-term cure of CL. [ABSTRACT FROM AUTHOR]

Abstract: Dengue virus (DENV) infections continue to spread aggressively around the world. Here we demonstrate that celgosivir (6-O-butanoyl castanospermine), strongly inhibits all four DENV serotypes. We show by fluorescence microscopy that the antiviral mechanism of celgosivir, is in part, due to misfolding and accumulation of DENV non-structural protein 1 (NS1) in the endoplasmic reticulum. Moreover, celgosivir modulates the host’s unfolded protein response (UPR) for its antiviral action. Significantly, celgosivir is effective in lethal challenge mouse models that recapitulate primary or secondary antibody-dependent enhanced DENV infection. Celgosivir treated mice showed enhanced survival, reduced viremia and robust immune response, as reflected by serum cytokine analysis. Importantly, survival increased even after treatment was delayed till 2days post-infection. Together the present study suggests that celgosivir, which has been clinically determined to be safe in humans, may be a valuable candidate for clinical testing in dengue patients. [Copyright &y& Elsevier]

Various studies have demonstrated that treatment with methyl prednisolone and chlorambucil could increase the chance of remission of idiopathic nephrotic syndrome (INS) of varied histology in patients who do not respond to the conventional treatment. This study was done to assess the safety and efficacy of methyl prednisolone and chlorambucil regimen in patients with various types of glomerulonephritides which were resistant to the usual conventional immunosuppressive drugs. Thirty nine patients were treated between June 1998 and December 2003 with Ponticelli regimen for six months. Twenty three patients (58.98%) were men and 16 (41.02%) were women. Mean age at the onset of NS was 23.59 ± 1.28 (range 10-51) years. Four patients (10.2%) had minimal change disease (MCD), six patients (15.4%) had membranoproliferative glomerulonephritis (MPGN), two (5.1%) had IgA nephropathy, and 18 patients (46.1%) had focal segmental glomerulosclerosis (FSGS). Eleven patients were excluded from the final analysis. Of the remaining 28 patients, mean baseline proteinuria was 3.31 ± 3.09 g/day. Mean baseline plasma albumin was 2.84 ± 1.002 g/dl and mean baseline serum creatinine was 0.87 ± 0.42 mg/dl. At the end of six months of treatment, mean proteinuria was 1.02 ± 0.85 g/day. Mean plasma albumin was 3.69 ± 0.78 g/day, and mean serum creatinine was 0.85 ± 0.26 mg/dl. Mean followup was 13.21 ± 7.7 times in 18.92 ± 12.58 months. At the end of six months of treatment, seven patients (25%) achieved complete remission (CR), 10 patients (35.71%) partial remission (PR), and 11 patients (39.3%) did not show any response to the therapy. Most of the patients in responder group had FSGS (64.70%), whereas in nonresponder group patients had MPGN and mesangioproliferative glomerulonephritis (MesPGN). Out of 13 FSGS cases five (38.46%) achieved CR, six (46.15%) PR, and only two (15.38%) failed to respond. The incidence of side effects was 39.3%. Responders had more side effects than nonresponders (47 vs 27.3%). Methyl prednisolone and chlorambucil therapy (Ponticelli regimen) is safe and efficacious in achieving remission in significant number of INS patients other than membranous nephropathy, without any serious side effect on short term followup. However, a longer followup is required to demonstrate the sustained efficacy and long-term side effect of this regimen. [ABSTRACT FROM AUTHOR]

Aim: To present and analyse the anatomical and functional outcomes for vitrectomy in Eales' disease. Methods: This retrospective case series enrolled 63 patients (71 eyes) who underwent pars plana vitrectomy (PPV) for the complications of Eales' disease. Indications included nonclearing vitreous haemorrhage (VH) with/without epiretinal membranes in 49 (69%) eyes, and retinal detachments (RD) involving/threatening macula in 22 (31%). Additional procedures (scleral buckling; gas/oil tamponade) were performed at surgeon's discretion. Minimum follow-up was 6 months. The primary outcome measures were change in best-corrected visual acuity (BCVA) and posterior segment status. Results: The mean age of the patients was 29.6 years (range: 15–70 years); 60 were male (95%). Preoperatively, posterior vitreous detachment (PVD) existed in 28 (39.4%) eyes. Forty (56.3%) eyes underwent only PPV; the rest required additional surgical procedures (q.v.). The mean baseline BCVA (1/60) improved to 6/24 postoperatively (P<0.0001). Fifty-four eyes of 50 patients (76%) showed an improvement of ≥2 equivalent Snellen lines; six eyes (four patients) remained stable (±1 line); visual acuity worsened in 11 eyes (nine patients). The mean final BCVA was similar in eyes operated for VH and RD (P=0.08); but the magnitude of change from baseline was greater in the VH group (P=0.009). PVD had a borderline association with final BCVA (P=0.056); but did not influence the functional/anatomical improvement. Thirteen eyes required repeat interventions; 11 (15.49%) eyes experienced surgical failure. Conclusions: Although surgical outcomes in Eales' disease depend on preoperative PVD/RD to some extent; good results are possible in the presence of incomplete PVD and tractional sequelae. Eye (2008) 22, 900–904; doi:10.1038/sj.eye.6702763; published online 30 March 2007 [ABSTRACT FROM AUTHOR]

Ramipril has been used in twice daily dose of 5 mg in most heart failure trials, whereas the dose used in Heart Outcomes Prevention Evaluation (HOPE) study was 10 mg once at bedtime. The HOPE investigators in an ambulatory blood pressure (ABP) substudy observed a fall of nighttime but not daytime blood pressure (BP). We examined the effects of once daily ramipril 10 mg versus 5 mg twice a day. Twenty-nine patients were recruited based on the original criteria for the HOPE study and were given ramipril either in twice-daily dose (5 mg b.d.) or once daily (10 mg o.d.) each morning in randomized, prospective crossover trial. Twenty-four hour ABP recordings were taken just before commencement of ramipril therapy and after treatment with twice-daily and once-daily ramipril. Our results show that ramipril causes a significant reduction of BP over 24-h period as compared with baseline. The mean baseline ABP was 124/73 mm Hg, which reduced to 117/69 mm Hg for the twice-a-day regimen (P<0.001) and 115/68 mm Hg for the once a day regimen (P<0.001). Both regimes effectively lower BP to a similar extent. Ramipril causes significant BP reduction in both once- and twice-daily dosing. The fall in BP after daytime dosing is greater than that observed in the HOPE study (including ABP substudy). Once-daily dosing in the morning seems to be effective in causing a significant reduction in the ABP profile of patients at high-risk of a future vascular event.Journal of Human Hypertension (2007) 21, 525–530; doi:10.1038/sj.jhh.1002174; published online 26 April 2007 [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a frequent infectious complication in patients on renal replacement therapy, as a result of immunosuppression from uremia and drugs in the post-transplantation period. A retrospective study of all renal transplantation patients from 1989 to date was conducted. This study tried to examine the prevalence, course, and outcome of TB in renal transplant recipients. A comparison with the occurrence of TB in other modalities of renal replacement therapy was also made. We also discussed the treatment protocols for TB in this group of patients. No difference in the prevalence, age, or male/female ratio of TB was seen among the 3 modes of renal replacement therapy. TB of the lung was the more favored site of infection in patients on hemodialysis (77.3%), when compared with those on CAPD (30%) and renal transplant recipients (33.3%). In renal transplant recipients, no deaths occurred due to TB. In 7 patients there was co-infection with cytomegalovirus and in 3 patients there was Aspergillus lung infection. [ABSTRACT FROM AUTHOR]

Open bite deformity following a successful midface advancement by distraction osteogenesis is a common complication. Temporary anchorage devices can be deployed during the distraction and post-distraction settling phases for restoring the occlusion even in severe cases. The following report describes the management of severe anterior open bite following maxillary distraction. [ABSTRACT FROM AUTHOR]