Recurrent disease after pediatric renal transplantation.

BACKGROUND: Recurrent disease after kidney transplant remains an important cause of allograft failure, accounting for 7-8% of graft loss and ranking as the fifth most common cause of allograft loss in the pediatric population. Although the pathophysiology of many recurrent diseases is incompletely understood, recent advances in basic science and therapeutics are improving outcomes and changing the course of several of these conditions. METHODS: Review of the literature. RESULTS: We discuss the diagnosis and management of recurrent disease. CONCLUSION: We highlight new insights into the pathophysiology and treatment of post-transplant primary hyperoxaluria, focal segmental glomerulosclerosis, immune complex glomerulonephritis, C3 glomerulopathy, lupus nephritis, atypical hemolytic uremic syndrome, and IgA nephropathy.

A Rational Approach To Antitubercular Drug Design: Molecular Docking, Prediction of ADME Properties and Evaluation of Antitubercular Activity of Novel Isonicotinamide Scaffold.

INTRODUCTION: One of the most devastating and leading diseases is Tuberculosis (TB), caused by Mycobacterium tuberculosis. Even though many synthetic drugs are available in the market, to increase the therapeutic efficacy and reduce toxicity. Isoniazid is the primary drug used in the treatment of tuberculosis. METHODS: The main objective of the study is to perform molecular docking studies and synthesize the derivatives of isonicotinamide along with the anti-tubercular activity. The isonicotinamide derivatives (a-j) are prepared using isoniazid, carbon disulphate, methyl cyanide, and benzaldehyde derivatives and characterized by TLC, IR, 1HNMR, and Mass spectroscopy. The enzyme decaprenylphosphoryl-D-ribose oxidase (DprE1) of M. tuberculosis had good binding capacity with all the ligands revealed in molecular docking studies. In-vitro studies indicated that all the ligands showed anti-tuberculosis with strain M. tuberculosis. RESULTS: The analysis was based on the binding energy and minimum inhibitory concentration (MIC). The highest and lowest binding energy is -4.22 Kcal/mol (f) and -8.45 Kcal/mol (d), and the MIC for compound d was found to be 644.22 nM. Among all the ligands, compound 5d has the most cytotoxic effect and lower IC50 values and better bioavailability. CONCLUSION: This investigation helps in the development of better anti-tubercular therapy.

Novel ibuprofen prodrug: A possible promising agent for the management of complications of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer's properties. Methods: Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet's test, p < 0.05 was considered to indicate the significance. Results: The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. Conclusion: The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

Comparative analysis of cheiloscopy, pulpal tissue and fingerprint for gender identification.

Background: The most important step in identifying an unknown person is determining one's gender and as a dentist, the oral tissues are potential sources of information in this aspect. A study was carried out to assess and evaluate the accuracy of cheiloscopy, pulp tissue, and fingerprints in determining gender. Material and Methods: A study comprising of 160 individuals (80 males and 80 females) was conducted. After obtaining informed written consent and recording their bio-data; lip prints, and fingerprints were recorded. The patients' extracted tooth was collected, their pulp extirpated, for assessment of the Barr body. Results: We found that every lip pattern was unique and hence can be used to identify an unknown individual. The occurrence of the Barr body was determined, and all female samples were found to be positive for the existence of the Barr body. In fingerprint patterns, a significant difference was noted between both sexes with ulnar loops and whorl patterns only. A highly significant difference was observed in the fingerprint ridge density between genders. Conclusions: We conclude that the Barr body in pulpal tissue can be considered as the best possible technique for gender determination within the dental tissues. Lip prints did not show any differences in genders and had no role to play in gender determination. Fingerprint ridge density can also be used to determine gender.

Assessment of potentially toxic elements in groundwater through interpolation, pollution indices, and chemometric techniques in Dehradun in Uttarakhand State.

Providing safe drinking water for the entire world's population is essential for ensuring sustainable development. The presence of harmful compounds in aquifers, majorly toxic elements, is a serious environmental concern around the globe. This research aimed to quantify for the initial period the amounts of toxic elements in freshwater in the Dehradun Industrial Region of Uttrakhand, India, as well as the associated health risks. The PTEs (potentially toxic elements) Fe, Cd, Mn, Cu, Cr and Pb, Zn, Ni is measured by AAS and compared to BIS and WHO requirements for drinking safety. The order of mean trace element values in all groundwater samples were determined as Fe > Zn > Cu > Ni > Co > Cd > Pb. HPI was discovered to be higher than high class during the research period (HPI > 30), but under the severe contamination criterion of 100. Iron's MI and PI values were consistently over the threshold limit during the research period, and certain toxic elements were discovered exceptionally near the threshold limit, indicating a severe future influence on groundwater quality. According to PCA (principal component analysis), CM (correlation matrix), and potential health hazard, maximum levels of toxic elements in groundwater in the Dehradun region are attributed to land use patterns, anthropogenic activity, industrial activity, fertilizer and pesticide leaching, and residential waste into the aquifer system. The findings of this study could aid local planners and policymakers in preventing health risks from contaminated aquifers through the deployment of suitable monitoring and mitigation measures.

Hydrochemical characterization of groundwater quality using chemometric analysis and water quality indices in the foothills of Himalayas.

Groundwater pollution of the watershed is mainly influenced by the multifaceted interactions of natural and anthropogenic process. To analyse the spatial-temporal variation and pollution source identification and apportionment, the dataset was subjected to a globally acknowledged coherent technique using water quality indices and chemometric techniques (principal component analysis (PCA) and cluster analysis. The bulk of the samples tested were below the BIS's permissible levels. Groundwater samples from the pre- and post-monsoon seasons mostly contained the anions HCO- 3 > Cl- > SO2- 4 > NO- 3, while the primary cations were Ca2+ > Mg2+ > Na+ > K+. Groundwater was alkaline and hard at most of the sites. According to hydro-geochemical facies and relationships, Piper diagrams, and principal component analysis, weathering, dissolution, leaching, ion exchange, and evaporation were the key mechanisms influencing groundwater quality. The hydrochemical facies classified the groundwater samples into the Ca-Mg-HCO3 type. For all the sampling locations, PIG was determined to be 0.43, 0.52, 0.47, 0.48, 1.00, and 0.70; respectively. The majority of the test locations fell into the low to medium contamination zone, as determined by the groundwater pollution index (PIG) and contamination index. Three principal components, which together account for 93.8% of the total variance, were identified via PCA. The study's findings confirm the value of these statistical techniques in interpreting and understanding large datasets and offering reliable information to reduce the time and expense of programmes for monitoring and evaluating water quality.

Deficiency of CFHR plasma proteins and autoantibody positive hemolytic uremic syndrome: treatment rationale, outcomes, and monitoring.

Deficiency of Complement Factor H Related (CFHR) plasma proteins and Autoantibody Positive Hemolytic Uremic Syndrome (DEAP-HUS) is a subtype of atypical hemolytic uremic syndrome, known to be associated with significant morbidity. Its pathogenesis is linked to the production of IgG autoantibodies against complement factor H, a regulator of the alternative complement pathway. The binding of the autoantibodies to the C terminal of complement factor H interferes with its regulatory function, leading to increased activation of the alternative complement pathway and consequent endothelial cellular damage. Early diagnosis and initiation of appropriate therapy is reported to lead to favorable outcomes. Institution of plasma exchange therapy within 24 h of diagnosis has been shown to rapidly lower antibody levels, leading to clinical improvement. Adjunctive immunosuppression therapy suppresses antibody production and helps in maintaining long-term clinical remission of the disease. Available data advocates a treatment regimen that combines plasma therapy (preferably plasma exchange) and immunosuppression to halt disease process and sustain long-term disease remission.

Real time detection and quantification of Epstein Barr virus in different grades of oral gingivitis and periodontitis patients.

BACKGROUND: Periodontal diseases are of microbial etiology and are globally causing loss of teeth in adult population. Many severe oral diseases have been recently associated to Herpes viruses, of which Epstein Barr Virus (EBV) and human cytomegalovirus (HCMV) have been indicated in the etiology of periodontal diseases. AIM: The purpose of the study was to compare the effect of EBV in different types of periodontal diseases namely acute gingivitis, chronic gingivitis, acute and chronic, localized and generalized aggressive (juvenile) periodontitis and apical periodontitis. MATERIAL AND METHOD: 70 individuals were included in this study. Supragingival plaque and plaque from two deepest sites of the periodontal pockets were collected then stored at 70° c and prepared for nucleic acid extraction. For EBV detection, DNA were extracted from the plaque samples with the QIAamp DNA mini kit. Q-PCR was performed by targeting the non-polymorphic Epstein-Barr nuclear antigen-1 (EBNA-1) gene using Corbett Research 6000 Q-PCR instrument and Rotor gene 6000 software. RESULTS: Overall prevalence of EBV in the disease group was 60% (27/45 patients) as compared to only 8% (4/25 people) in the normal population. The mean copy number of EBV DNA was found to be significantly higher in periodontitis (2234 ± 1811.34) when compared to gingivitis (554 ± 537.64, p = .001) and normal patients (370 ± 161.03, p < .001). CONCLUSION: Here, we found that the prevalence of EBV as well as copy number of EBV was significantly higher in periodontitis patients as compared to gingivitis patients or normal population.

Does Oral Submucous Fibrosis Affect the Hearing Ability of an Individual? A Cross-Sectional Study in North Indian Population

Abstract Objective: To evaluate the hearing efficiency of Oral Submucous Fibrosis (OSF) patients using Pure Tone Audiometry (PTA) and to correlate between the hearing efficiency and clinical stage of OSF. Material and Methods: Twenty-five patients clinically diagnosed as OSF were evaluated for hearing loss using 'PTA'. Patients were grouped as mild cases and severe cases. Mild cases comprised of Group A and B, and severe cases comprised of Group C and D. Patients suffering from the previous hearing were excluded from the study. The data were submitted to statistical evaluation using the Chi-square test. The level of significance was set at 5% Results: Out of the total patients, 52.4% were diagnosed as mild cases (Group M) OSF and 47.6% as severe cases (Group S). The analysis of the data of mild cases and severe cases revealed a significant association between advancing stages of OSF and hearing loss (p = 0.026). The cases in Group M after otoscopic evaluation demonstrated no visible ear defect. However, 30% of cases in Group S showed retraction of the tympanic membrane Conclusion: The results indicate an association between stages of OSF and hearing loss. With advancing stages of OSF, there may be involvement of muscles of soft palate namely the levator veli palatine or tensor veli palatine, which may lead to the narrowing of the Eustachian tube leading to a decrease in air conduction demonstrating it as hearing loss of varying degrees depending upon the involvement.

Oral squamous papilloma occurring on the palate with review of literature.

Squamous papillomas are common lesions occurring on skin, oral and nasal mucosa and male and female genital organs. Oral squamous cell papilloma (OSP) is a benign proliferation of the stratified squamous epithelium and is generally believed to be caused by Human Papilloma Viruses (HPV). It constitutes around 2.5% of all oral verruco-papillary lesions. We here, report a case of palatal OSP occurring in a 55-year-old male. The aetiological, clinical, diagnostic and treatment aspects of OSP are discussed here.

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection.

BACKGROUND: Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric kidney transplant patients. METHODS: We examined seven patients with treatment-refractory C4d + AMR. Immunosuppression included antithymocyte globulin or anti-CD25 monoclonal antibody for induction therapy with maintenance corticosteroids, calcineurin inhibitor, and anti-metabolite. Estimated glomerular filtration rate (eGFR) calculated by the Schwartz equation, biopsy findings assessed by 2013 Banff criteria, and human leukocyte antigen (HLA) donor-specific antibodies (DSA) performed using the Luminex single antigen bead assay were monitored pre- and post- bortezomib therapy. RESULTS: Seven patients (86 % male, 86 % with ≥6/8 HLA mismatch, and 14 % with pre-formed DSA) age 5 to 19 (median 15) years developed refractory C4d + AMR between 1 and 145 (median 65) months post-transplantation. All patients tolerated bortezomib. One patient had allograft loss. Of the six patients with surviving grafts (86 %), mean pre-bortezomib eGFR was 42 ml/min/1.73 m(2) and the mean 1 year post-bortezomib eGFR was 53 ml/min/1.73 m(2). Five of seven (71 %) had improvement of histological findings of AMR, C4d staining, and/or acute cellular rejection. Reduction in HLA DSAs was more effective for class I than class II. CONCLUSIONS: Bortezomib appears safe and may correlate with stabilization of eGFR in pediatric kidney transplant patients with refractory C4d + AMR.

Multiple myeloma with an unusual oral presentation.

Multiple myeloma (MM) is a dyscrasia caused by neoplastic proliferation of somatically mutated plasma cells. Myeloma cells divide and expand within the bone marrow affecting multiple locations in the body where bone marrow is present. Oral manifestations, though common are usually not diagnosed. This report describes rare oral manifestations of multiple myeloma like oral petechiae and gingival swelling presented in a 40-year-old male patient. The diagnosis was established by blood examination & skeletal survey, while oral findings were later correlated with the diagnosis of MM. A brief review on MM is presented along with the demonstration of rare oral manifestations.

Optimizing HLA matching in a highly sensitized pediatric patient using ABO-incompatible and paired exchange kidney transplantation.

BACKGROUND: Kidney transplantation is the treatment of choice for end-stage renal disease. However, since pediatric patients have long projected life-years, it is also optimal for them to get well-matched transplants to minimize long-term sensitization. In North America, pediatric kidney transplantation is largely dependent upon the use of deceased donor organs, making it challenging to identify timely, well-matched transplants. Pediatric recipients may have willing living donors who are either HLA- or ABO-incompatible (ABOi); therefore, one solution is to utilize ABOi transplants and paired exchange programs to enhance HLA matching and living donation. CASE-DIAGNOSIS/TREATMENT: We adopted this approach for a highly sensitized patient with cPRA 90%, who received a successful ABOi paired exchange transplant. The recipient received pre-transplant immunomodulation until an acceptable isohemagglutinin titer <1:8 was reached before transplantation. The patient was induced with anti-thymocyte globulin and maintained on steroid-based triple immunosuppression. Eighteen-month allograft function is excellent with an estimated glomerular filtration rate (eGFR) of 83.53 ml/min/1.73 m(2). The patient did not develop de novo donor-specific HLA antibodies or have any episodes of acute rejection CONCLUSIONS: This case highlights the safety and efficacy of using paired exchange in combination with ABOi transplants in pediatric kidney transplantation to optimize HLA matching, minimize wait times, and enhance allograft survival.

External Inflammatory Root Resorption in Mandibular First Molar: A Case Report.

External root resorption (ERR) is an irreversible loss of external tooth structure. Its etiology is multifactorial, but in many aspects remain unclear. Periapical inflammation sustained by infection can cause apical root resorption in permanent teeth. The infection may be asymptomatic for many years, although it is rarely misdiagnosed. Treatment of such lesions should include use of intracanal medicaments for complete debridement of the microbes. Here, we present a case of 21-year-old male patient who presented with external inflammatory root resorption.

High-resolution, whole-body vascular imaging with ferumoxytol as an alternative to gadolinium agents in a pediatric chronic kidney disease cohort.

BACKGROUND: Exposure to gadolinium-based contrast agents (GBCA) in patients with chronic kidney disease (CKD) has been associated with the development of a potentially fatal disorder, nephrogenic systemic fibrosis (NSF). Although contrast-enhanced computed tomography (CT) is an alternative to magnetic resonance imaging (MRI), it carries the risk of radiation exposure and further reduction of residual renal function. Therefore we sought to assess the feasibility of ferumoxytol as an alternative to GBCA for contrast-enhanced MR angiography (MRA) in a pediatric cohort with CKD. Ferumoxytol is a parenteral iron supplement that contains ultrasmall superparamagnetic iron oxide (USPIO) and is a potent relaxivity agent for MRI. METHODS: We describe the MRI findings in ten pediatric patients who needed detailed vascular mapping. Ferumoxytol (4 mg/kg) was administered intravenously for contrast-enhanced MRA. The patients tolerated the procedure without complications. RESULTS: Resulting studies were highly diagnostic and were pivotal in guiding patient management. The images were notable for clear delineation of multiple vascular occlusions. CONCLUSIONS: Given the concerns associated with the use of GBCAs in renal failure, ferumoxytol is an excellent alternative contrast agent in pediatric end stage renal disease (ESRD) patients. Future studies are needed in order to further evaluate safety and efficacy of ferumoxytol in this patient population.

Suppression of iron-regulatory hepcidin by vitamin D.

The antibacterial protein hepcidin regulates the absorption, tissue distribution, and extracellular concentration of iron by suppressing ferroportin-mediated export of cellular iron. In CKD, elevated hepcidin and vitamin D deficiency are associated with anemia. Therefore, we explored a possible role for vitamin D in iron homeostasis. Treatment of cultured hepatocytes or monocytes with prohormone 25-hydroxyvitamin D or active 1,25-dihydroxyvitamin D decreased expression of hepcidin mRNA by 0.5-fold, contrasting the stimulatory effect of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D on related antibacterial proteins such as cathelicidin. Promoter-reporter and chromatin immunoprecipitation analyses indicated that direct transcriptional suppression of hepcidin gene (HAMP) expression mediated by 1,25-dihydroxyvitamin D binding to the vitamin D receptor caused the decrease in hepcidin mRNA levels. Suppression of HAMP expression was associated with a concomitant increase in expression of the cellular target for hepcidin, ferroportin protein, and decreased expression of the intracellular iron marker ferritin. In a pilot study with healthy volunteers, supplementation with a single oral dose of vitamin D (100,000 IU vitamin D2) increased serum levels of 25D-hydroxyvitamin D from 27±2 ng/ml before supplementation to 44±3 ng/ml after supplementation (P<0.001). This response was associated with a 34% decrease in circulating levels of hepcidin within 24 hours of vitamin D supplementation (P<0.05). These data show that vitamin D is a potent regulator of the hepcidin-ferroportin axis in humans and highlight a potential new strategy for the management of anemia in patients with low vitamin D and/or CKD.

In Vitro and In Vivo Study of Poly(ethylene glycol) Conjugated Ibuprofen to Extend the Duration of Action.

Ibuprofen-polyethylene glycol (PEG) conjugates (PEG-Ibu) were prepared and their potential as a prolonged release system was investigated. Two PEG-Ibu conjugates were synthesized from Ibuprofen and PEG with two different molecular weights by esterification in the presence of DCC and DMAP. The PEG-Ibu conjugates were characterized by FT-IR, (1)H NMR, Mass spectroscopy and DSC analysis. The solubility study in aqueous system showed an increase in solubility of conjugates. The dissolution / hydrolysis studies showed a specific acid-base catalysis pattern dependent on the pH of the medium. This indicated a good chemical stability in aqueous buffer solution of acidic medium and the extended release behavior was found in both prodrugs after 9 hour. The results demonstrate that, in the same condition, the rate of hydrolysis for PEG(4000)-Ibu is slower than other. The Writhing induced by acetic acid experiment and paw edema test after oral administration showed that both conjugates had extended analgesic and anti-inflammatory effects compared with Ibuprofen. These results suggest that PEG-Ibu could be a promising NSAID prodrug with an extended pharmacological effect owing to delayed-release of parent drug.