Pattern of renal and urinary tract disorders in children

Background: Pediatricians encounter a wide spectrum of renal and urinary tract ailments in children most of which cause considerable morbidity and mortality in children. Such disorders are seen in children of all age groups starting right from infancy up till adolescence. The aim of our study was to study the prevalence, spectrum and clinical profile of such disorders in children. Methods: This was a hospital based prospective observational study conducted over a period of 12 months from September 2017 to September 2018 at G. B. Pant hospital and Sher-i-Kashmir Institute of Medical Sciences Srinagar. Children presenting with renal and urinary tract disorders between the age group of 1 month and 12 years were prospectively observed and recorded. Results: Total number of patients between age group 1month to 12 years admitted with renal and urinary tract disorders were 197. Majority of patients i.e. 56 (28.4%) were less than one year old. Mean±SD age of patients was 3.9±3.41 years. Fever was the most common complaint present in 78 patients (39.6%).  Urinary tract infection was the most common diagnosis in our study comprising of 71 (36%) patients followed by nephrotic syndrome in 39 (19.8%). Other diagnosis were congenital anomalies of kidney and urinary tract- CAKUT (13.2%), acute glomerulonephritis-AGN (10.2%), Acute kidney injury- AKI (9.1%), chronic kidney disease- CKD in 9 (4.6%) and tubular disorders (4.1%). Conclusions: Because of their significant prevalence and impact on the quality of life, renal and urinary tract disorders require prompt diagnosis and management because early detection and treatment improves the morbidity and mortality

Modulation of Antibody Responses to the V1V2 and V3 Regions of HIV-1 Envelope by Immune Complex Vaccines

Prophylactic HIV vaccines must elicit antibodies (Abs) against the virus envelope glycoproteins (Env) to effectively prevent HIV infection. We investigated a vaccine platform that utilizes immune complexes made of Env proteins gp120 and monoclonal Abs (mAbs) against different gp120 epitopes. We previously observed alterations in V3 antigenicity upon formation of certain gp120/mAb complexes and demonstrated the ability of these complexes to modulate the elicitation of V3 Ab responses. However, the effects on the V1V2 domain, an important target for Abs that correlate with vaccine-induced protection against HIV, have not been studied, nor have immune complex vaccines made with non-B subtype Env. This study compared subtypes B (JRFL) and CRF_01.AE (A244) Env gp120 proteins in complex with selected gp120-specific mAbs. Allosteric and antigenic changes were detected on these immune complexes, indicating that gp120/mAb interaction induces alterations on the Env surface that may modify the Env immunogenic properties. To evaluate this idea, mice were immunized with gp120/mAb complexes or their uncomplexed gp120 counterparts. The overall serum IgG titers elicited against gp120 were comparable, but a marked skewing toward V1V2 or V3 was evident and dependent on the gp120 strain and the specificity of the mAb used to form the complexes. Compared with uncomplexed gp120JRFL, gp120JRFL complexed with CD4bs or V1V2 mAbs, but not with C2 or V3 mAbs, elicited V3 Abs of greater titers and breadth, and Abs more capable of neutralizing tier 1 virus. Epitope mapping revealed a shift to a more conserved site in the V3 crown. However, the complexes did not enhance V1V2 Ab response, and the elicited V1V2 Abs were not cross-reactive. This profile contrasts with Ab responses to gp120A244/mAb complexes. Notably, gp120A244/mAb complexes induced higher levels of V1V2 Abs with some cross-reactivity, while also stimulating weak or strain-specific V3 Abs. Sera from gp120A244/mAb complex-immunized animals displayed no measurable virus neutralization but did mediate Ab-dependent cellular phagocytosis, albeit at levels similar to that induced by gp120A244 alone. These data indicate the potential utility of immune complexes as vaccines to shape Ab responses toward or away from Env sites of interest

Primary tuberculous gingival enlargement - A rare clinical entity: Case report and brief review of the literature

Tuberculosis (TB) is a chronic specific granulomatous disease and a major cause of death in developing countries. The clinical presentation of TB lesions of the oral cavity varies widely and can manifest as ulcerations, diffuse inflammatory lesions, granulomas and fissures. Oral lesions generally appear secondary to primary TB infection elsewhere, although primary infection of the oral mucosa by Mycobacterium tuberculosis has also been described. We hereby report a case of primary TB of the gingiva manifesting as gingival enlargement. Diagnosis was based on histopathological examination, complete blood count, X-ray chest and immunological investigations with detection of antibodies against M. tuberculosis. Anti-tuberculous therapy was carried out for over 6 months and was followed by surgical excision of the residual enlargement under local anesthesia. After 1-year follow-up, there was no recurrence of the disease. This case report emphasizes the need for dentists to include TB in the differential diagnosis of various types of gingival enlargements

Heterogeneity in glycan composition on the surface of HIV-1 envelope determines virus sensitivity to lectins.

Lectins that target N-glycans on the surface of HIV-1 envelope (Env) glycoprotein have the potential for use as antiviral agents. Although progress has been made in deciphering the molecular details of lectin and Env glycan interaction, further studies are needed to better understand Env glycan heterogeneity among HIV-1 isolates and its influence on virus-neutralization sensitivity to lectins. This study evaluated a panel of lectins with fine specificity for distinct oligosaccharides and assessed their ability to inhibit infection of HIV-1 viruses known to have differing sensitivity to anti-HIV Env antibodies. The results showed that HIV-1 isolates have different sensitivity to lectins specific for α1-3Man, α1-6Man, and α1-2Man binding lectins. Considering that lectins exclusively recognize the oligosaccharide components of virus Env, these data suggest that glycan heterogeneity among HIV-1 isolates may explain this differential sensitivity. To evaluate this further, chronic and acute viruses were produced in the presence of different glycosidase inhibitors to express more homogenous glycans. Viruses enriched for α1-2Man terminating Man5-9GlcNAc2 glycans became similarly sensitive to α1-2Man-binding lectins. The α1-3Man- and α1-6Man-binding lectins also were more potent against viruses expressing predominantly Man5GlcNAc2 and hybrid type glycans with terminal α1-3Man and α1-6Man. Furthermore, lectin-mediated inhibition was competitively alleviated by mannan and this effect was augmented by enrichment of mannose-type glycans on the virus. In addition, while Env of viruses enriched with mannose-type glycans were sensitive to Endo-H deglycosylation, Env of untreated viruses were partially resistant, indicating that HIV-1 Env glycans are heterogeneously comprised of complex, hybrid, and mannose types. Overall, our data demonstrate that HIV-1 isolates display differential sensitivity to lectins, in part due to the microheterogeneity of N-linked glycans expressed on the surface of the virus Env glycoprotein

Chronic Kidney Disease in Children: A Review

Chronic kidney disease (CKD) in children is a life-consuming ailment with a variable but progressive course. CKD, in particular, the end stage kidney disease (ESKD) affects multiple body systems complexed with secondary complications that significantly and adversely affect the growth, development and quality of life. Although uncommon in children, CKD poses unique challenges to the health care delivery system to manage the primary renal disorders and extrarenal manifestations of CKD along with a heavy socioeconomic burden. Despite the availability of better management tools, there is a rise in incidence and prevalence of pediatric CKD for which wide range short- and long-term planning is inevitable that will lure the medicos to acquire the advanced nephrological training and skills, besides providing quality infrastructure and sustained socio-economic support. Our review is aimed to provide recent advances regarding the evaluation and management of pediatric CKD and its complications

Defensive role of Rosmarinus officinalis in carbon tetrachloride-induced nephrotoxicity and oxidative stress in rats

Abstract Background There is a growing demand for remedies from natural sources to substitute synthetic therapeutic drugs and minimize their side effects and toxicity. The present study aims to evaluate the defensive ability of an ethanolic extract of Rosmarinus officinalis L. in carbon tetrachloride (CCl4)-induced nephrotoxicity in male albino rats. Materials and methods Thirty-six rats were divided into 6 groups (n = 6). Group I (control) received distilled water for 30 days orally. Nephrotoxicity was induced by CCl4 (11% v/v with olive oil, i.p) 2 ml/kg body weight (b.wt.) in group II once a week for 30 days. Groups III and IV received the only herb in two doses 100 and 250 mg/kg of b.wt. respectively. Groups V and VI received an ethanolic extract of Rosmarinus officinalis (EERO, 100 and 250 mg/kg of b.wt.) along with 2 ml/kg b.wt. CCl4 weekly for 30 days. Results CCl4 treatment induced highly significant (P < 0.001) elevation in kidney biomarkers, i.e., blood urea nitrogen and creatinine, kidney biochemicals, i.e., LPO and XOD, and decrease the levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione in tissue. However, EERO significantly (P < 0.001) restored the altered levels of these biomarkers in a dose-dependent manner. Furthermore, EERO also prevents histological alteration caused due to the toxicity of CCl4. Conclusion Our findings strongly support that ethanolic extract of Rosmarinus officinalis acts as a potent scavenger of free radicals to prevent the toxic effect of CCl4 and hence validate its ethnomedicinal use

Deglycosylation of wild type vs glycan-modified Envs by Endo-H and PNGase F.

<p>a) JRFL viruses were produced in 293T cells with kifunensine or swansonine or in GnTI-/- cells, concentrated from culture supernatants by Lenti X-100, and then treated (+) or not treated (-) with Endo H to remove high-mannose and hybrid-mannose <i>N</i>-glycans but not complex <i>N</i>-glycans. b) JRFL viruses were similarly produced and treated with (+) or without (-) PNGase F to remove all <i>N</i>-glycans. The digestion products were subjected to SDS-PAGE under a reduced condition and Western blot analysis with anti-gp120 mAbs. Untreated Env gp120 and enzyme treated Env gp120 are indicated by black and red arrows, respectively.</p

Virus inhibition by lectins that differ in oligosaccharide specificity.

<p>Lectins were tested to block infection of HIV-1 pseudoviruses SF162.LS (tier 1A), Bal.01 (tier 1B), JRFL.JB (tier 2, chronic), and REJO4541.67 (tier 2, acute) in TZM-bl cells. Lectins were serially diluted, added to viruses (200 TCID₅₀), and incubated for 1 h at 37°C before addition of TZM-bl cells. After 48 h, virus infection was measured by β-galactosidase activity. Cell viability was measured in parallel using CellTiter Glow kit (Promega). Experiments were performed four times; averages and standard deviations from all experiments are shown.</p

Effect of glycan modification of HIV-1 envelope on sensitivity to lectins.

<p>Effect of glycan modification of HIV-1 envelope on sensitivity to lectins.</p

Effect of <i>N</i>-glycan modification on virus sensitivity to lectins.

<p>JRFL.JB and REJO4541.67 viruses were produced in 293T cells in the presence of glycosylation-pathway inhibitors kifunensine or swainsonine, or in 293S GnTI^-/- cells lacking GlcNAc transferase I. Lectins were serially diluted; viruses were then added at 200 TCID₅₀ and incubated for 1 h at 37°C before addition of TZM-bl cells. After 48 h, virus infection was measured based on β-galactosidase activity. Cells infected with viruses only, in the absence of lectins, represent 100% infection. Percentage of virus inhibition by lectin was calculated using virus control (virus and cells only, 0% inhibition) and cell control (cell and no virus, 100% inhibition). All experiments were performed in duplicate and repeated three times. Data are shown as the averages and standard deviations from all 3 experiments.</p