Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats

The development and progression of diabetic nephropathy is dependent on glucose homeostasis and many other contributing factors. In the present study, we examined the effect of nitecapone, an inhibitor of the dopamine-metabolizing enzyme catechol-O-methyl transferase (COMT) and a potent antioxidant, on functional and cellular determinants of renal function in rats with streptozotocin-induced diabetes. Administration of nitecapone to diabetic rats normalized urinary sodium excretion in a manner consistent with the dopamine-dependent inhibition of proximal tubule Na,K-ATPase activity. Hyperfiltration, focal glomerulosclerosis, and albuminuria were also reversed by nitecapone, but in a manner that is more readily attributed to the antioxidant potential of the agent. A pattern of elevated oxidative stress, measured as CuZn superoxide dismutase gene expression and thiobarbituric acid-reactive substance content, was noted in diabetic rats, and both parameters were normalized by nitecapone treatment. In diabetic rats, activation of glomerular protein kinase C (PKC) was confirmed by isoform-specific translocation and Ser23 phosphorylation of the PKC substrate Na,K-ATPase. PKC-dependent changes in Na,K-ATPase phosphorylation were associated with decreased glomerular Na,K-ATPase activity. Nitecapone-treated diabetic rats were protected from these intracellular modifications. The combined results suggest that the COMT-inhibitory and antioxidant properties of nitecapone provide a protective therapy against the development of diabetic nephropathy.     

Favorable prognosis for patients 12 to 18 months of age with stage 4 nonamplified MYCN neuroblastoma: a Children's Cancer Group Study.

PURPOSE: The long-term survival of children between age 12 and 24 months with stage 4 neuroblastoma and nonamplified MYCN (MYCN-NA) has not been defined previously. PATIENTS AND METHODS: Survival for stage 4 MYCN-NA neuroblastoma patients enrolled onto Children's Cancer Group (CCG) protocols 321P2 (1986 to 1991) and 3891 (1991 to 1996) was analyzed. Treatment consisted of intensive alkylator-based induction chemotherapy with or without autologous bone marrow transplantation (ABMT) with or without 13 cis-retinoic acid. Survival was analyzed by age strata less than 12, 12 to 18, 18 to 24, and more than 24 months at diagnosis. Patients younger than 12 months were treated on the moderate-intensity CCG protocol 3881. RESULTS: Forty-three patients with stage 4 MYCN-NA disease enrolled onto CCG-321P2 (n = 17) or CCG-3891 (n = 26) were between 12 and 24 months of age at diagnosis. After a median follow-up of 94 months (range, 4 to 140 months), the 6-year event-free survival (EFS) for the 12- to 18-month age group was superior to that of the 18- to 24-month age group (74% +/- 8% v 31% +/- 12%; P = .008). The EFS for children older than 24 months with stage 4 MYCN-NA neuroblastoma was 23% +/- 3%, and for children younger than 12 months was 92% +/- 3%. CONCLUSION: Children diagnosed with stage 4 MYCN-NA neuroblastoma in the second year of life form a transitional group between infants and older children in terms of prognosis. Patients between 12 and 18 months of age have significantly better long-term survival than that of older children treated with intensive chemotherapy with or without ABMT. These patients may not benefit from additional intensification of therapy beyond that provided in earlier clinical trials and may even maintain this high survival rate with less intensive therapy.     

Osteogenic pulmonary metastases originating from a phyllodes tumour of the breast with osteosarcomatous differentiation

Malignant phyllodes tumour is an uncommon breast neoplasm which undergoes osteosarcomatous differentiation in 1.3% of cases. We document the plain film, CT and scintigraphic features of a case of pulmonary metastases from this rare primary tumour.     

Synthesis and Structure-Activity Relationships of Vasicine Analogues as Bronchodilatory Agents

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 13-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect.     

Geographic contiguity and genetic affinity among five ethnic populations of Manipur,India: further molecular studies based on VNTR and STR loci

Background : Apart from traditional markers studied among a few numerically small, geographically defined surveys among Mongoloid populations in northeastern parts of India, very little is known about their genomic diversity at the molecular level. Primary objective : This study seeks to investigate how best the variable number tandem repeat (VNTR) and short tandem repeat (STR) loci together can detect the patterns of the genetic affinity among five geographically contiguous, linguistically and socio-culturally diverse Mongoloid-affiliated populations of Manipur in northeastern regions of India. Subject and methods : Blood samples were collected from unrelated and randomly selected volunteers of five ethnic populations (Meitei, Kuki, Naga, Hmar and Manipuri Muslim) from different parts of the state. Allelic variation in four minisatellite loci (D1S7, D4S139, D5S110 and D17S79) and three STR loci (vWA, FESFPS and F13AO1) was studied. Results : Average heterozygosity values among the five groups for the minisatellite range from 68% to 94%, while the hypervariable three STR loci were between 60% and 88%. In the populations, all the studied loci were highly polymorphic, with almost no departure from Hardy-Weinberg equilibrium. The gene differentiation for the VNTR loci was lower and moderate ( G st = 0.030) in comparison with microsatellites ( G st = 0.043). The neighbour-joining method of clustering based on both type of molecular markers reveals a close cluster for the tribal groups of Kuki, Naga and Hmar, while Manipur Muslim stand distinct in both the trees. The clustering pattern obtained from the combined DNA marker loci matches more closely the pattern from STR loci than that obtained from VNTR loci. Conclusions : The results reinforce that using both VNTR and STR loci in detecting regional genetic affinity among the populations is more effective than using VNTR or STR independently, and also confirm the results obtained from the serological and electrophoretic data. However, the clustering pattern obtained from combined DNA markers is more in conformity with the pattern obtained by STR loci rather than with VNTR loci. Despite linguistic, geographical and cultural barriers, the populations show genetic affinity among the four populations except in the case of the migrant Manipur Muslim group.     

A systematic review of IT for diabetes self-management: Are we there yet?

BackgroundRecent advances in information technology (IT) coupled with the increased ubiquitous nature of information technology (IT) present unique opportunities for improving diabetes self-management. The objective of this paper is to determine, in a systematic review, how IT has been used to improve self-management for adults with Type 1 and Type 2 diabetes.MethodsThe review covers articles extracted from relevant databases using search terms related information technology and diabetes self-management published after 1970 until August 2012. Additional articles were extracted using the citation map in Web of Science. Articles representing original research describing the use of IT as an enabler for self-management tasks performed by the patient are included in the final analysis.ResultsOverall, 74% of studies showed some form of added benefit, 13% articles showed no-significant value provided by IT, and 13% of articles did not clearly define the added benefit due to IT. Information technologies used included the Internet (47%), cellular phones (32%), telemedicine (12%), and decision support techniques (9%). Limitations and research gaps identified include usability, real-time feedback, integration with provider electronic medical record (EMR), as well as analytics and decision support capabilities.ConclusionThere is a distinct need for more comprehensive interventions, in which several technologies are integrated in order to be able to manage chronic conditions such as diabetes. Such IT interventions should be theoretically founded and should rely on principles of user-centered and socio-technical design in its planning, design and implementation. Moreover, the effectiveness of self-management systems should be assessed along multiple dimensions: motivation for self-management, long-term adherence, cost, adoption, satisfaction and outcomes as a final result.     

Impaired anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with diabetes mellitus: A preliminary report

Background and aimsPatients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM).MethodsRecords of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis.ResultsThirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA_1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14–17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019).ConclusionsCOVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.