Regression of Dalton’s lymphoma in vivo via decline in lactate dehydrogenase and induction of apoptosis by a ruthenium(II)-complex containing 4-carboxy <Emphasis Type="Italic">N</Emphasis>-ethylbenzamide as ligand

A novel ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide (Ru(II)-CNEB) was found to interact with and inhibit M4-lactate dehydrogenase (M4-LDH), a tumor growth supportive enzyme, at the tissue level. The present article describes modulation of M4-LDH by this compound in a T-cell lymphoma (Dalton’s Lymphoma: DL) vis a vis regression of the tumor in vivo. The compound showed a dose dependent cytotoxicity to DL cells in vitro. When a non toxic dose (10 mg/kg bw i.p.) of Ru(II)-CNEB was administered to DL bearing mice, it also produced a significant decline in DL cell viability in vivo. The DL cells from Ru(II)-CNEB treated DL mice showed a significant decline in the level of M4-LDH with a concomitant release of this protein in the cell free ascitic fluid. A significant increase of nuclear DNA fragmentation in DL cells from Ru(II)-CNEB treated DL mice also coincided with the release of mitochondrial cytochrome c in those DL cells. Importantly, neither blood based biochemical markers of liver damage nor the normal patterns of LDH isozymes in other tissues were affected due to the treatment of DL mice with the compound. These results were also comparable with the effects of cisplatin (an anticancer drug) observed simultaneously on DL mice. The findings suggest that Ru(II)-CNEB is able to regress Dalton’s lymphoma in vivo via declining M4-LDH and inducing mitochondrial dysfunction–apoptosis pathway without producing any toxicity to the normal tissues.     

A case of human thelaziasis from Himachal Pradesh

Small, chalky-white, threadlike, motile worms were isolated from the conjunctival sac of a 32 year-old woman residing in the Himalaya mountains. They were identified as both male and female worms of Thelazia callipaeda. To the best of our knowledge, this is the second case report of human thelaziasis from India.     

Normal human fibroblasts exposed to high- or low-dose ionizing radiation: differential effects on mitochondrial protein import and membrane potential

How oxidative metabolism modulates effects of ionizing radiation is incompletely understood. Because mitochondria participate in oxidative metabolism, we investigated the modulation of mitochondrial protein import and membrane potential (DeltaPsi) in irradiated cells. Our data show that effects at low dose cannot be predicted from effects at high dose. When density-inhibited normal human fibroblasts were exposed to a toxic dose of 4 Gy, protein import into mitochondria isolated from these cells was decreased. In contrast, protein import into mitochondria isolated from low-dose-irradiated (10 cGy) cells was enhanced, suggesting that mitochondria may play a crucial role in low-dose-induced adaptive responses. At high dose, import defects were not solely due to changes in mitochondrial DeltaPsi, and modulation of import was not tightly linked to the cellular capacity to repair radiation damage. Another striking observation is that in proliferating nonirradiated cells, mitochondrial protein import and DeltaPsi were regulated in a cell cycle-dependent manner, being lower in S phase than in G (1). Interestingly, when quiescent G (0)/G (1) phase cells exposed to high-dose radiation were stimulated to proliferate, events associated with S phase, but not G (1), significantly affected import. The strategy described here may serve as novel end points to study radiation-induced effects.     

Odontoclastoma

Case report showing classical odontoclastoma along with in vivo illustrations of the affected tooth and intral oral periapical radiograph.     

A comparative evaluation of newer sedatives in conscious sedation

This double blind study was undertaken to determine the safety and efficacy of orally administered newer sedatives and analgesics for conscious sedation in 120 child patients. Patients were randomly assigned into: Midazolam (I), Ketamine (II), Zolpidem (III), Midazolam plus Ketamine (IV), Midazolam plus Tramadol (V) and Zolpidem plus Tramadol (VI) groups of 20 each. Onset of action, level of sedation, ease of treatment completion, recovery time, and post-operative amnesia were assessed for all and compared. Midazolam plus ketamine was found the most effective combination providing a fast and adequate analgo-sedation in anxious and uncooperative child patients.     

C5a receptor‐deficient dendritic cells promote induction of Treg and Th17 cells

C5a is a proinflammatory mediator that has recently been shown to regulate adaptive immune responses. Here we demonstrate that C5a receptor (C5aR) signaling in DC affects the development of Treg and Th17 cells. Genetic ablation or pharmacological targeting of the C5aR in spleen‐derived DC results in increased production of TGF‐β leading to de novo differentiation of Foxp3⁺ Treg within 12 h after co‐incubation with CD4⁺ T cells from DO11.10/RAG2^?/? mice. Stimulation of C5aR^?/? DC with OVA and TLR2 ligand Pam₃CSK₄ increased TGF‐β production and induced high levels of IL‐6 and IL‐23 but only minor amounts of IL‐12 leading to differentiation of Th cells producing IL‐17A and IL‐21. Th17 differentiation was also found in vivo after adoptive transfer of CD4⁺ Th cell into C5aR^?/? mice immunized with OVA and Pam₃CSK₄. The altered cytokine production of C5aR^?/? DC was associated with low steady state MHC class II expression and an impaired ability to upregulate CD86 and CD40 in response to TLR2. Our data suggest critical roles for C5aR in Treg and Th17‐cell differentiation through regulation of DC function.     

Totally implantable venous access ports: Retrospective review of long-term complications in 81 patients

Aim of The Study: A totally implantable venous access port (TIVAP) has become an essential prerequisite for many chemotherapy protocols. It is serving its purpose very well, but its use is not without complications. We are presenting our experience with these devices (TIVAPs). Subjects and Methods: We retrospectively reviewed the totally implantable venous access ports in 81 patients at our hospital between January 2009 and March 2011 for long-term problems which include postoperative and follow-up problems, excluding the immediate complications which occur at the time of insertion. Results: Catheter malfunction was the most common complication (9.87%, 0.40/1000 device-days of use/observation). Catheter-related bloodstream infections were present in 5 (6.17%) patients (0.25/1000 device-days of use/observation). The mean life of the catheter was 246 days. Only 11.1% ports required removal during the treatment period. Overall, patients either completed treatment (82.8%) or died (6.1%) while receiving treatment. Conclusion: TIVAPs provide safe and reliable vascular access for patients on chemotherapy but require utmost care by a dedicated team of trained medical professionals and paramedics experienced with the use of such ports, in order to minimize the complications and their continued use while administering treatment.     

ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression

Recurrent somatic ASXL1 mutations occur in patients with myelodysplastic syndrome, myeloproliferative neoplasms, and acute myeloid leukemia, and are associated with adverse outcome. Despite the genetic and clinical data implicating ASXL1 mutations in myeloid malignancies, the mechanisms of transformation by ASXL1 mutations are not understood. Here, we identify that ASXL1 mutations result in loss of polycomb repressive complex 2 (PRC2)-mediated histone H3 lysine 27 (H3K27) tri-methylation. Through integration of microarray data with genome-wide histone modification ChIP-Seq data, we identify targets of ASXL1 repression, including the posterior HOXA cluster that is known to contribute to myeloid transformation. We demonstrate that ASXL1 associates with the PRC2, and that loss of ASXL1 in?vivo collaborates with NRASG12D to promote myeloid leukemogenesis.     

Integration of leprosy into GHS in India: a follow up study (2006-2007)

In India leprosy services, were integrated into the General Health Services (GHS), in a phased manner, in different provinces, from 2001 to 2004. This study reports the findings from a follow-up operational research undertaken in 2006-2007, to assess the level of integration, on predetermined indicators related to: referral services, training of health functionaries, availability of diagnosis, treatment, MDT dispersal and counselling guidelines in health facilities, recording and reporting by GHS staff, MDT stock management and involvement of health sub-centres in different Indian provinces. Nine provinces, 18 districts, 88 health facilities and 108 sub-centres were selected, by using multistage stratified random sampling techniques. Reverse integration, as reflected by the training and deployment of vertical staff in GHS, was also assessed. Data was collected by medical officers experienced in leprosy, with the assistance of state health functionaries, and recorded on separate schedules for health facility and sub-centre levels. The study also touched on the issue of client perception towards MDT services by interviewing 149 under treatment/cured leprosy cases (who had completed treatment within the last year), in the community with the help of local interpreters. Results showed wide variations across the selected provinces in various parameters. District leprosy nuclei were understaffed in 12(66.7%) districts, and district hospitals were not working as referral institutions anywhere. The training status of medical officers and multi-purpose workers in leprosy was low in Andhra Pradesh (6.9 and 22.4%), Madhya Pradesh (26.3 and 14.5%), Rajasthan (19.7 and 40.9%) and Kerala (25.5 and 65.7%). MDT stock availability as per the National Leprosy Eradication Programme (NLEP) guidelines was not adequate in all provinces. Availability of patient counseling guidelines was nil/low in Kerala, Karnataka, West Bengal, Orissa, Rajasthan and Andhra Pradesh. The involvement of sub-centres, in case referral, recording and dispensing MDT was nil Kerala and Rajasthan and poor in Andhra Pradesh. Ninety percent of clients in Kerala and 38.0% in Andhra Pradesh and Madhya Pradesh did not get MDT in the nearest health facilities or sub-centres.