COVID 19 infection associated with thrombotic thrombocytopenic purpura

Journal of Thrombosis and Thrombolysis - Thrombotic thrombocytopenic purpura (TTP) which can cause significant mortality is a thrombotic microangiopathy due to deficiency of VWF cleaving protease...     

Detection and characterization of HIV type 2 in Calcutta, India

Since the first report of HIV/AIDS in India in 1986, continuous serosurveillance has been undertaken in all Indian states. Recently, five cases of HIV-2 infection have been detected in Calcutta, situated in the eastern part of India. The full-length envelope gene (2.5 kb) of one of the strains was amplified, cloned, and sequenced. Phylogenetic analysis of the Calcutta HIV-2 envelope revealed a close relatedness to the HIV-2 Rod sequence isolated in offshore Senegal. This strain, however, showed a genetic diversity of 13.5% to other Indian HIV-2 isolates.     

Effect of brain monoamines on the secretion of adrenocorticotrophic hormone

The role of brain monoamines (5-HT, NA and DA) in the secretion of adrenocorticotrophic hormone (ACTH) was studied in view of contradictory reports. Plasma corticosterone levels and the rate of synthesis of corticosterone in vitro by the adrenal gland were estimated in albino rats and have been taken as the index of ACTH activity. These estimations were done in unstressed and stressed, and in untreated and treated rats. Drugs were administered intracerebroventricularly to the rats to cause selective degeneration of tryptaminergic, noradrenergic or dopaminergic neurons. The results show that plasma corticosterone levels and the rate of synthesis of corticosterone were significantly decreased after selective degeneration of tryptaminergic neurons in unstressed rats. After selective degeneration of either tryptaminergic or noradrenergic neurons, the acute increase in the plasma corticosterone levels and rate of synthesis of corticosterone in vitro by adrenal glands in stressed rats were significantly inhibited. These results have been interpreted to suggest that the central tonic control on adrenal glands may be 5-HT mediated and that during stress ACTH secretion may be both 5-HT and NA mediated. DA does not seem to have significant role in the regulation of ACTH secretion.     

Stimulation of serotonin2 receptors in the ventrolateral medulla of the cat results in nonuniform increases in sympathetic outflow

Topical application of the serotonin2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane or DOI, in a dose of 30 micrograms/side to the intermediate area of the ventrolateral surface of the medulla produced a significant increase in mean arterial pressure with no significant change in heart rate both in intact animals (n = 8) and in cervically vagotomized animals (n = 3). The pressor response of DOI was blocked by pretreatment of the intermediate area with ketanserin, a serotonin2 antagonist (n = 7). Pretreatment with intravenous phentolamine did not block the pressor response of DOI (n = 3). However, this pressor response could be counteracted by intravenous propranolol (n = 5) or by bilateral stellate ganglionectomy (n = 3). These data suggest that sympathoexcitation by centrally applied DOI selectively increased cardiac inotropy but not chronotropy. Further studies indicate that DOI increased contractile force without increasing heart rate and that the positive inotropic effect of DOI could be counteracted by bilateral stellate ganglionectomy. Bilateral microinjections of DOI into the subretrofacial nucleus in a dose of 100 ng (n = 3) and a dose of 300 ng (n = 3) increased mean arterial blood pressure by 23 +/- 2 and 44 +/- 6 mm Hg, respectively, without producing any changes in heart rate. These data suggest that DOI has a central site of action in the ventrolateral medulla, presumably at the subretrofacial nucleus, which leads to selective sympathoexcitation of the cardiac ventricles.     

Prophylactic Dose of Neem (Azadirachta indica) Leaf Preparation Restricting Murine Tumor Growth is Nontoxic,Hematostimulatory and Immunostimulatory

Significant restriction of growth of Ehrlich's carcinoma was observed following prophylactic treatment on Swiss albino mice with neem leaf preparation (NLP-1 unit) once weekly for four weeks. Toxic effects of this particular dose (1 unit), along with 0.5 unit and 2 units of NLP doses, were evaluated on different murine physiological systems. One hundred percent of mice could tolerate 4 injections of 0.5 and 1 unit NLP doses. Body weight, different organ-body weight ratios and physical behavior of treated mice remained completely unchanged during treatment with different NLP doses. All of these NLP doses were observed to stimulate hematological systems as evidenced by the increase in total count of RBC, WBC and platelets and hemoglobin percentage. As histological changes as well as elevation in serum alkaline phosphatase, SGOT, SGPT were not observed in mice treated with three different doses of NLP, the nonhepatotoxic nature of NLP was proved. The level of serum urea remained unaltered and normal architecture of the cortical and medullary parts of the kidney were also preserved after NLP treatment. Increased antibody production against B16 melanoma antigen was detected in mice immunized with 0.5 unit and 1 unit of NLP. Number of splenic T lymphocytes (CD4+ and CD8+) and NK cells were also observed to be increased in mice injected with 0.5 unit and 1 unit of NLP. However, NLP dose of 2 units could not exhibit such immunostimulatory changes; NLP mediated immunostimulation was correlated well with the growth restriction of murine carcinoma. In other words, tumor growth restriction was observed only when mice were injected with immunostimulatory doses of NLP (0.5 unit and 1 unit).     

Evaluation and evolution of apparent diffusion coefficient (ADC) in image-guided adaptive brachytherapy (IGABT) for cervical cancer

PURPOSEImage-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging–derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy.Methods and MaterialsThirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge.ResultsThe measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10^?3 mm²/s, respectively. The TBadc (ADC at brachytherapy, center), TEBadc (tumor edge ADC at brachytherapy), and TE1cmBadc (1 cm from edge brachytherapy) were 1.2, 1.8, and 2.3 × 10^?3 mm²/s, respectively, p-value <0.00001. No abnormal ADC was present outside the high-risk clinical target volume contours.ConclusionMRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.     

Retrograde Mitochondrial Transport Is Essential for Organelle Distribution and Health in Zebrafish Neurons

In neurons, mitochondria are transported by molecular motors throughout the cell to form and maintain functional neural connections. These organelles have many critical functions in neurons and are of high interest as their dysfunction is associated with disease. While the mechanics and impact of anterograde mitochondrial movement toward axon terminals are beginning to be understood, the frequency and function of retrograde (cell body directed) mitochondrial transport in neurons are still largely unexplored. While existing evidence indicates that some mitochondria are retrogradely transported for degradation in the cell body, the precise impact of disrupting retrograde transport on the organelles and the axon was unknown. Using long-term, in vivo imaging, we examined mitochondrial motility in zebrafish sensory and motor axons. We show that retrograde transport of mitochondria from axon terminals allows replacement of the axon terminal population within a day. By tracking these organelles, we show that not all mitochondria that leave the axon terminal are degraded; rather, they persist over several days. Disrupting retrograde mitochondrial flux in neurons leads to accumulation of aged organelles in axon terminals and loss of cell body mitochondria. Assays of neural circuit activity demonstrated that disrupting mitochondrial transport and function has no effect on sensory axon terminal activity but does negatively impact motor neuron axons. Taken together, our work supports a previously unappreciated role for retrograde mitochondrial transport in the maintenance of a homeostatic distribution of mitochondria in neurons and illustrates the downstream effects of disrupting this process on sensory and motor circuits.SIGNIFICANCE STATEMENT Disrupted mitochondrial transport has been linked to neurodegenerative disease. Retrograde transport of this organelle has been implicated in turnover of aged organelles through lysosomal degradation in the cell body. Consistent with this, we provide evidence that retrograde mitochondrial transport is important for removing aged organelles from axons; however, we show that these organelles are not solely degraded, rather they persist in neurons for days. Disrupting retrograde mitochondrial transport impacts the homeostatic distribution of mitochondria throughout the neuron and the function of motor, but not sensory, axon synapses. Together, our work shows the conserved reliance on retrograde mitochondrial transport for maintaining a healthy mitochondrial pool in neurons and illustrates the disparate effects of disrupting this process on sensory versus motor circuits.     

To study the clinical efficacy and nephrotoxicity along with the risk factors for acute kidney injury associated with parenteral polymyxin B

Aim:

The aim of this study was to evaluate the clinical efficacy and nephrotoxicity along with the risk factors for acute kidney injury (AKI) associated with the parenteral polymyxin B in patients with the multidrug resistance (MDR) gram −ve infections in a tertiary Intensive care unit (ICU).

Materials and Methods:

A retrospective cohort study (March 2010-October 2011) was conducted in Medical ICU of a 23 bedded tertiary care hospital in Northern India.

Results:

Out of 71 ICU patients who were administered polymyxin B, only 32 (M:F = 1:0.8) met the inclusion criteria. Patients with concurrent administration of nephrotoxic drugs were excluded from the study. Mean age of patients was 48.53 ± 13.90 years ranging from 16 years to 68 years. 6 out of 32 (18.7%) patients progressed to AKI, whereas renal functions remained normal in 26 (81.2%) patients. No statistically significant difference was observed in mortality between AKI and non AKI patients at the end of therapy (33.3% vs. 26.9%, P value 0.756). Older age (62.33 ± 11.90 vs. 45.34 ± 2.45, P value 0.005) was found to be an independent risk factor for causing nephrotoxicity.

Conclusion:

In the present scenario of rising infections with MDR gram −ve micro-organisms, this pilot study suggests that polymyxin B can be used effectively and safely in patients not receiving other nephrotoxic drugs, with cautious administration in older patients as they are more vulnerable to nephrotoxicity caused by polymyxin B.     

A new begomovirus–betasatellite complex is associated with chilli leaf curl disease in Sri Lanka

Leaf curl disease of chilli (LCDC) is a major constraint in production of chilli in the Indian subcontinent. The objective of this study was to identify the begomovirus species occurring in chilli in Sri Lanka, where the LCDC was initially recorded in 1938. The virus samples were collected from the North Central Province, the major chilli growing region in Sri Lanka with a history of epidemic prevalence of LCDC. The virus could be readily transmitted by Bemisia tabaci to chilli, tomato and tobacco, where vein clearing followed by leaf curl developed. The genome analysis of two isolates obtained from two distantly located fields showing 100 % LCDC, revealed that the DNA-A genome (2754 nucleotides) shared 89.5 % sequence identity with each other and 68.80–84.40 % sequence identity with the other begomoviruses occurring in the Indian subcontinent. The closest identity (84.40 %) of the virus isolates was with Tomato leaf curl Sri Lanka virus (ToLCLKV). The results support that a new begomovirus species is affecting chilli in Sri Lanka and the name Chilli leaf curl Sri Lanka virus (ChiLCSLV) is proposed. Recombination analysis indicated that ChiLCSLV was a recombinant virus potentially originated from the begomoviruses prevailing in southern India and Sri Lanka. The genome of betasatellite associated with the two isolates consisted of 1366 and 1371 nucleotides and shared 95.2 % sequence identity with each other and 41.50–73.70 % sequence identity with the other betasatellite species. The results suggest that a new begomovirus betasatellite, Chilli leaf curl Sri Lanka betasatellite is associated with LCDC in Sri Lanka. This study demonstrates a new species of begomovirus and betasatellite complex is occurring in chilli in Sri Lanka and further shows that diverse begomovirus species are affecting chilli production in the Indian subcontinent.