Review of photoresponsive and glycoside dendrimers in biomaterials and sensors applications

Dendrimers are branched molecules with well-defined lengths, shapes, molecular weights, and monodispersity in comparison to linear polymers. The dual effect of the chromophore luminescence and the morphology of the synthesized dendrimers has drawn a lot of interest towards the design of dendrimers with different chromophores. Furthermore, the stimulus-responsive systems can sequester drug molecules under a preset set of parameters and release them in a different environment in response to either an exogenous or endogenous stimulus. The addition of photoresponsive moieties to different dendrimer components, such as the core or branches, magnifies the importance of the dendrimer in several related sectors of nanotechnology, such as sensors, photoswitches, electronic gadgets, and drug delivery systems. This review article focused on photoresponsive/glycoside dendrimer structures and their biomaterial applications.

Dendrimers are branched molecules with well-defined lengths, shapes, molecular weights, and monodispersity in comparison to linear polymers.     

Intestinal epithelial cell-specific CD98 expression regulates tumorigenesis in Apc(Min/+) mice

The transmembrane glycoprotein CD98 regulates integrin signaling that in turn controls cell proliferation and survival. CD98 expression is upregulated in various carcinomas, including colorectal cancer. Recently, by generating gain- and loss-of-function mouse models featuring genetic manipulation of CD98 expression specifically in intestinal epithelial cells (IECs), we have explored the crucial role of CD98 in the regulation of intestinal homeostasis and inflammation-associated tumorigenesis. In the present study, we investigated the contribution of CD98 to intestinal tumorigenesis in Apc(Min/+) mice and the underlying mechanism of action. Mice featuring IEC-specific CD98 overexpression (Tg animals) were crossed with Apc(Min/+) mice, and the characteristics of intestinal adenoma formation were assessed. Compared with Apc(Min/+) mice, Tg/Apc(Min/+) animals exhibited increases in both intestinal tumor incidence and tumor size; these parameters correlated with enhanced proliferation and decreased apoptosis of IECs. IEC-specific CD98 overexpression resulted in increased synthesis of the oncogenic proteins c-myc and cyclin-D1 in Apc(Min/+) mice, independently of the Wnt-APC-β-catenin pathway, suggesting the implication of CD98 overexpression-mediated Erk activation. IEC-specific CD98 overexpression enhanced the production of proinflammatory cytokines and chemokines that are crucial for tumorigenesis. We validated our results in mice exhibiting IEC-specific CD98 downregulation (CD98(flox/+)VillinCre animals). IEC-specific CD98 downregulation efficiently attenuated tumor incidence and growth in Apc(Min/+) mice. The reduction of intestinal tumorigenesis upon IEC-specific CD98 downregulation was caused by the attenuation of IEC proliferation and cytokine/chemokine production. In conclusion, we show that CD98 exerts an oncogenic activity in terms of intestinal tumorigenesis, via an ability to regulate tumor growth and survival.     

Chemometrics of differentially expressed proteins from colorectal cancer patients

AIM:To evaluate the usefulness of differentially expressed proteins from colorectal cancer (CRC) tissues for differentiating cancer and normal tissues.METHODS:A Proteomic approach was used to identify the differentially expressed proteins between CRC and normal tissues.The proteins were extracted using Tris buffer and thiourea lysis buffer (TLB) for extraction of aqueous soluble and membrane-associated proteins,respectively.Chemometrics,namely principal component analysis (PCA) and linear discriminant analy...     

Renal transplantation in the elderly: South Indian experience

In developing countries, renal transplantation is offered to young end-stage renal disease (ESRD) patients, while the older ones face limitations due to higher mortality risk. We retrospectively analyzed 225 patients who underwent renal transplantation from living donors, aged 40–60 years (Group A) and >60 years (Group B), focusing on their survival outcome. Group A (n = 181) had mean creatinine (mg/dL) 1.41 ± 0.84, 1.30 ± 0.65 and 1.40 ± 0.60 and mean eGFR (mL/min/1.73 m²) of 65.32 ± 23.03, 69.14 ± 32.65 and 59.21 ± 22.79 at 0, 3 and 6 months post-transplantation. Death-censored graft survival was 93.1% in first year followed by 91.2% in subsequent 4 years. Patient survival was 92.5% in first year, 90.7% in the next 2 years, and 89.2% in 4th year. Highest cumulative graft survival was 86.7% in the first year with 83.4%, 82.7% and 82.4% during the subsequent 3 years. Group B (n = 44) had mean creatinine (mg/dL) of 1.46 ± 1.02, 1.29 ± 0.23 and 1.2 ± 0.29 with a mean eGFR (mL/min/1.73 m²) of 67.90 ± 23.48, 67.02 ± 12.76 and 75.23 ± 15.19 at 0, 3 and 6 months. Highest death-censored graft survival was 97.4% in the first year with 94.7% in next 3 years. Patient survival was 88.1% throughout 4 years post-transplantation. Cumulative graft survival was 84.1% during 4 years. Biopsy-proven acute rejection rate was 28.7% in group A and 15.9% in group B (P = 0.058). There was higher mortality rate in group B with death mainly due to infections and cardiovascular complication. Cardiovascular risk assessment, pre-transplant cancer screening and judicious use of immunosuppressive agents should help minimize adverse events, balanced with an inherently reduced risk of acute rejection, hence the graft survival advantage and is the way forward to maximize patient and renal allograft survival in elderly patients.     

Anaemia in rheumatoid arthritis: can we afford to ignore it?

INTRODUCTION Anaemia is common in rheumatoid arthritis (RA). Clinicians may focus on rheumatological issues and assume anaemia of chronic disease (ACD). This study challenged this assumption and investigated the causes of anaemia in a large cohort of RA patients to assess its implications. METHODS The hospital where the study was conducted monitors regular full blood count and erythrocyte sedimentation rate (ESR) monthly in all RA patients on disease modifying drugs to assess efficacy and safety. A computerised system identifies and records abnormal results. The database for 2009 was interrogated to find all patients with two consecutive haemoglobin values <11 g/dl. Using a proforma, patients were defined as having iron deficiency anaemia (IDA), ACD, macrocytic anaemia (MCA) or another cause. All results of further tests investigating the anaemia were recorded. RESULTS Among 2000 RA patients on the system, 199 (10%) were identified as having anaemia over a year. Of these, 90 had IDA, 78 had ACD, 25 had MCA, and 6 had postoperative anaemia. Among 90 patients with IDA, investigations were performed in 53, with 23 normal. An explanation for IDA was found in 30: gastrointestinal bleeding in 25, gynaecological blood loss in 3, and urinary bleeding in 2. Among 78 patients with ACD, response to intensification of RA treatment occurred in 45, but erythropoietin therapy was required in 9. Within the 25 patients with MCA, 12 had unrecognised vitamin B(12) deficiency, 4 drug induced changes, 3 myeloid malignancy, 2 hypothyroidism, and 2 alcoholism. CONCLUSIONS Anaemia in RA is common, multifactorial, and potentially both serious and correctable. Established malignancy was present in 10 patients and premalignancy in a further 10 (10% of total). Treatable causes were commonly identified. Clinicians need to investigate the nature and cause of persistent anaemia, and must not assume it to be simply ACD without evidence.     

A rare cause of intermittent dysphagia: giant fibrovascular polyp of the proximal esophagus

Fibrovascular polyps account for only 0.5-1% of all benign esophageal tumors and causes intermittent dysphagia. The patient was a 63-year-old gentleman with gradually progressive intermittent dysphagia of 40 days duration. Investigations revealed a submucosal tumor of the proximal esophagus causing luminal compromise. Excision was performed through a cervical esophagotomy and specimen was subject to histopathological examination. Postoperative recovery was uneventful and he was completely relieved of his symptoms.     

Long-Term Outcome of Adults Who Undergo Transplantation with Single Pediatric Kidneys: How Young Is too Young?

Background and objectives: The optimal donor age for transplanting a single pediatric kidney in an adult recipient remains unknown. En block kidney transplantation is usually performed when the donor age is <5 yr.Design, setting, participants, & measurements: We compared the outcomes of adult patients who underwent transplantation with single pediatric kidneys from donors who were younger than 5 yr (group 1, n = 40) and from donors who were aged 5 to 10 yr of age (group 2, n = 39) in our center.Results: The donor kidney sizes were significantly smaller in group 1 than in group 2 (P < 0.001), and group 1 required more ureteral stents than group 2 (73 versus 38%). The surgical complications, delayed graft function, and development of proteinuria were similar in both groups. Group 1 had slightly higher rejection episodes than group 2 (25 versus 18%; P = 0.67), and graft function was comparable in both groups. There were no statistical differences between the two groups in patient (P = 0.73) or death-censored graft (P = 0.68) survivals over 5 yr.Conclusions: Single pediatric kidney transplants from donors who are younger than 5 yr can be used with acceptable complications and long-term outcomes as those from older donors.Transplantation of en block pediatric kidneys into an adult was first performed in 1972 (1). Giving both pediatric kidneys instead of one theoretically provides sufficient nephron mass to an adult body. Good long-term graft survival has been demonstrated (2,3). Splitting en block kidneys and transplanting a single pediatric kidney into each recipient could potentially increase kidney transplants. Mixed results have been reported (4–9). The technical concerns of vascular and ureteral complications (4,5,10,11) and the medical concerns of delayed graft function (DGF), rejection, and hyperfiltration injury have been raised (4,8,12).The minimum donor age or body weight that allows successfully splitting en block kidneys for adult recipients remains controversial. Registry data reported worse outcomes in single pediatric kidney transplants than en block transplants from donors who were younger than 5 yr or weighed <21 kg (2,3). As a result, en block transplantation has generally been considered the “preferred” method when donor age is <5 yr (2). In this study, we summarize our experience using single pediatric kidneys from donors who were younger than 5 yr. We compare the posttransplantation complications and the long-term outcomes of adult patients who underwent transplantation with single pediatric kidneys from donors who were younger than 5 yr with those who underwent transplantation with single kidneys from donors who were older than 5 but younger than 10 yr.     

Calcific Constrictive Pericarditis With Refractory Hypokalemia in a Patient With Gitelman’s Syndrome

Calcific constrictive pericarditis can be idiopathic or associated with radiation therapy, surgery, infection, or autoimmune disorders. Gitelman’s syndrome is a distal renal tubular defect involving the thiazide-sensitive luminal sodium chloride cotransporter and has been associated with nephrolithiasis and chondrocalcinosis. There has not been any case of calcific constrictive pericarditis reported so far in association with Gitelman’s syndrome. We have reported a male patient with persistent hypokalemia and refractory ascites diagnosed with calcific constrictive pericarditis and Gitelman’s syndrome.