Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

The use of ABO-incompatible grafts in living donor liver transplantation—First report from India

ABO incompatibility is the commonest reason for rejection of donors in living donor liver transplantation (LDLT). The donor pool could be expanded by 25 % to 35 % if the ABO barrier is overcome. In the absence of pre-conditioning, transplantation across the blood groups is fraught with the almost universal risk of antibody-mediated rejection (AMR) that rapidly leads to graft loss. However, AMR can be prevented by removal of preformed antibodies and reducing their production by B cells. We describe our initial experience of three cases of ABO-incompatible (ABO-i) LDLT: a 42-year-old male, an 8-month-old male and a 28-month-old female, all of blood group O+ who received blood group B + right lobe, B + left lateral segment, and A + left lateral segment liver grafts, respectively. Pre-LDLT conditioning included administration of anti-CD20 antibody (Rituximab^®) to the adult 4 weeks prior, and four to seven sessions of double-filtration plasmapheresis to all, to remove preformed antibodies and achieve anti-donor blood group antibody (ADA) titers of ≤1:16 IgG and ≤1:8 IgM, respectively. In addition, cases 1 and 3 received mycophenolate mofetil for 7 days prior to LDLT. After LDLT, all three patients achieved normal graft function over 8–17 days with no evidence of AMR and without the need for further plasmapheresis. Postoperative complications included portal vein thrombosis (one successfully re-explored), CMV (one), Pseudomonas and Klebsiella sepsis (one each), and abdominal collection (one treated with percutaneous drainage). All are currently well with normal graft function and low ADA titers at 8, 16, and 19 months after ABO-i LDLT.     

Triphala inhibits alpha-synuclein fibrillization and their interaction study by NMR provides insights into the self-association of the protein

The process of assembly and accumulation of the intrinsically disordered protein (IDP), alpha-synuclein (αSyn) into amyloid fibrils is a pathogenic process leading to several neurodegenerative disorders such as Parkinson''s disease, multiple system atrophy and others. Although several molecules are known to inhibit αSyn fibrillization, the mechanism of inhibition is just beginning to emerge. Here, we report the inhibition of fibrillization of αSyn by Triphala, a herbal preparation in the traditional Indian medical system of Ayurveda. Triphala was found to be a rich source of polyphenols which are known to act as amyloid inhibitors. ThT fluorescence and TEM studies showed that Triphala inhibited the fibrillization of αSyn. However, it was observed that Triphala does not disaggregate preformed αSyn fibrils. Further, native-PAGE showed that Triphala reduces the propensity of αSyn to oligomerize during the lag phase of fibrillization. Our NMR results showed that certain stretches of residues in the N-terminal and NAC regions of αSyn play an anchor role in the self-association process of the protein, thereby providing mechanistic insights into the early events during αSyn fibrillization.

Triphala inhibits αSyn self-association by interacting with anchoring regions which are responsible for αSyn oligomerization.     

Electrolyte and Haemogram changes post large volume liposuction comparing two different tumescent solutions

Background:

The most common definitions of large volume liposuction refer to total 5 l volume aspiration during a single procedure (fat plus wetting solution). Profound haemodynamic and metabolic alterations can accompany large volume liposuction. Due to paucity of literature on the effect of different tumescent solutions on the electrolyte balance and haematological changes during large volume liposuction, we carried out this study using two different wetting solutions to study the same.

Materials and Methods:

Total 30 patients presenting with varying degrees of localized lipodystrophy in different body regions were enrolled for the study. Prospective randomized controlled trial was conducted by Department of Plastic and Cosmetic Surgery, Sir Ganga Ram Hospital, New Delhi from January 2011 to June 2012. Patients were randomized into two groups of 15 patients each by using computer generated random numbers. Tumescent formula used for Group A (normal saline [NS]) was our modification of Klein''s Formula and Tumescent formula used for Group B (ringer lactate [RL]) was our modification of Hunstadt''s formula. Serum electrolytes and hematocrit levels were done at preinduction, immediate postoperative period and postoperative day 1.

Result:

Statistical analysis was performed using SPSS software version 15.0. Which showed statistically significant electrolytes and hematocrit changes occur during large volume liposuction.

Conclusion:

Statistically significant electrolytes and hematocrit changes occur during large volume liposuction and patients should be kept under observation of anaesthesist for at least 24 h. Patients require strict monitoring of vital parameters and usually Intensive Care Unit is not required. There was no statistical difference in the electrolyte changes using NS or RL as tumescent solution and both solutions were found safe for large volume liposuction.KEY WORDS: Electrolyte changes during liposuction, haemogram changes during liposuction, large volume liposuction     

Distally based posterior tibial artery perforator flap for coverage of defects around the ankle,heel and lower third of leg

Introduction

Reconstruction of distal leg region remained a difficult task. Free flaps had long been considered as a gold standard for these regions. However, due to various limitations of the free flap, a local fasciocutaneous flap could be considered as a good alternative. In this study, the use of a distally based posterior tibial artery perforator flap had been evaluated in the coverage of defects around the ankle, heel, and lower third of a leg. The study also outlined the donor-site morbidity and the technical details of the surgical procedure.

Methods

In this prospective study, a total of 42 patients with distal lower leg defects were included. The defects were located on the lower third of the leg (n?=?23), ankle (n?=?11), and heel (n?=?8). Reconstruction was performed using distally pedicled posterior tibial artery perforator flaps. Patients were evaluated in terms of viability of the flap, functional gain, and donor-site morbidity. The technical details of the operative procedure have also been outlined.

Results

All the flaps survived well, with the exception of one patient, who experienced complete flap loss. Minor complications were, however, noted in four other patients: One patient developed superficial epidermolysis; one developed postoperative venous congestion, which subsided within 3 days by conservative means, and in two patients, partial loss of the skin graft occurred at the donor site but healed completely with dressing and antibiotics. The patients were followed up for an average period of 6 months, ranging from 1 to 13 months. Donor-site morbidity was minimal.

Conclusions

It was concluded that the distally based pedicled posterior tibial artery perforator flap was a reliable, easy, less time-consuming, and versatile procedure for covering the defects around the ankle, heel, and lower third a leg. Level of Evidence: Level IV, therapeutic study     

Duplex PCR Assay for Identification of Tissue of Cattle and Buffalo Origin Targeting Mitochondrial Cytochrome b Gene

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The aim of this study was to develop PCR assay for simultaneous detection of tissues from cattle and buffalo...     

SARS-CoV-2 and Influenza Virus Co-Infection Cases Identified through ILI/SARI Sentinel Surveillance: A Pan-India Report

SARS-CoV-2/influenza virus co-infection studies have focused on hospitalized patients who usually had grave sequelae. Here, we report SARS-CoV-2/influenza virus co-infection cases from both community and hospital settings reported through integrated ILI/SARI (Influenza Like Illness/Severe Acute Respiratory Infection) sentinel surveillance established by the Indian Council of Medical Research. We describe the disease progression and outcomes in these cases. Out of 13,467 samples tested from 4 July 2021–31 January 2022, only 5 (0.04%) were of SARS-CoV-2/influenza virus co-infection from 3 different sites in distinct geographic regions. Of these, three patients with extremes of age required hospital admission, but none required ICU admission or mechanical ventilation. No mortality was reported. The other two co-infection cases from community settings were managed at home. This is the first report on SARS-CoV-2/Influenza virus co-infection from community as well as hospital settings in India and shows that influenza viruses are circulating in the community even during COVID-19. The results emphasize the need for continuous surveillance for multiple respiratory pathogens for effective public health management of ILI/SARI cases in line with the WHO (World Health Organization) recommendations.