The Protective Effect of L-carnitine on Ionizing Radiation-induced Free Oxygen Radicals

Ionizing radiation is known to generate reactive oxygen species (ROS) that can be removed by antioxidants.  L-carnitine, a natural component of mammalian tissue, is a necessary factor in the utilization of long-chain  fatty acids to produce energy. Furthermore it has been shown that L-carnitine is an antioxidant which has  a scavenger effect on ROS and a stabilizing effect on damaged cell membranes. The aim of the study was  to evaluate the potential protective effect of L-carnitine on radiation-induced free radicals in hamsters. Lcarnitine  was given by gavage at a dose of 50 mg/kg for 15 consecutive days before irradiation with a single  dose of 8 Gy. 24 h after radiation exposure, the hamsters were sacrificed and samples were taken from  blood and tissues, and the biochemical and histopatological determinations were carried out. In the irradiated  group, there were significant increases in plasma and liver malondialdehyde (MDA) with marked  reduction in glutathione (GSH) levels in the liver, compared with controls. In red blood cells, superoxide  dismutase (SOD) and catalase activities were also reduced. All these effects were reversed by L-carnitine.  In conclusion, L-carnitine with its antioxidant and free radical scavenging properties could play a modulatory  role against the cellular damage produced by free radicals induced by ionizing radiation.

Nanoengineering of a Negative-Index Binary-Staircase Lens for the Optics Regime

We show that a binary-staircase optical element can be engineered to exhibit an effective negative index of refraction, thereby expanding the range of optical properties theoretically available for future optoelectronic devices. The mechanism for achieving a negative-index lens is based on exploiting the periodicity of the surface corrugation. By designing and nanofabricating a plano-concave binary-staircase lens in the InP/InGaAsP platform, we have experimentally demonstrated at 1.55 microns that such negative-index concave lenses can focus plane waves. The beam propagation in the lens was studied experimentally and was in excellent agreement with the three-dimensional finite-difference time-domain numerical simulations.Comment: 4 pages, 4 figure

Healing Potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration.

<p>Abstract</p> <p>Background</p> <p>The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, <it>Picrorhiza kurroa </it>in healing indomethacin-induced acute stomach ulceration in mice and examine its capacity to modulate oxidative stress and the levels of prostaglandin (PGE₂) and EGF during the process.</p> <p>Methods</p> <p>Male swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose) were treated up to 7 days with different doses of the methanol extract of <it>P. kurroa </it>rhizomes (designated as PK). The healing capacity of the most effective dose of PK (20 mg/kg, p. o. × 3 d) was compared with that of omeprazole (Omez) (3 mg/kg, p. o. × 3 d). The effects of the drug-treatment for one and three days on the biochemical parameters were assessed by comparing the results with that of untreated mice of the 1^stand 3^rdday of ulceration. The stomach tissues of the mice were used for the biochemical analysis.</p> <p>Results</p> <p>The macroscopic indices revealed maximum ulceration on the 3^rdday after indomethacin administration, which was effectively healed by PK. Under the optimized treatment regime, PK and Omez reduced the ulcer indices by 45.1% (<it>P </it>< 0.01), and 76.3% respectively (<it>P </it>< 0.001), compared to the untreated ulcerated mice.</p> <p>Compared to the ulcerated untreated mice, those treated with PK for 3 days showed decreased the levels of thiobarbituric acid reactive substances (TBARS) (32.7%, <it>P </it>< 0.05) and protein carbonyl (37.7%, <it>P </it>< 0.001), and increased mucin (42.2%, <it>P </it>< 0.01), mucosal PGE₂(21.4%, <it>P </it>< 0.05), and expressions of COX-1 and 2 (26.9% and 18.5%, <it>P </it>< 0.05), EGF (149.0%, <it>P </it>< 0.001) and VEGF (56.9%, <it>P </it>< 0.01). Omez reduced the TBARS (29.4%, <it>P </it>< 0.05), and protein carbonyl (38.9%, <it>P </it>< 0.001), and increased mucin (38.3%, <it>P </it>< 0.01), without altering the other parameters significantly.</p> <p>Conclusion</p> <p>PK (20 mg/kg, p. o. × 3 days) could effectively heal indomethacin-induced stomach ulceration in mice by reducing oxidative stress, and promoting mucin secretion, prostaglandin synthesis and augmenting expressions of cyclooxygenase enzymes and growth factors.</p

Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.

Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. HCT is a definitive cure for DADA2 with &gt; 95% survival

Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency : Report on 30 Patients

Correction; Early Access: ' DOI: 10.1007/s10875-022-01280-y Early Access: APR 2022Purpose Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-alpha) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. Methods We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Results Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. Conclusion HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. Clinical Implications HCT is a definitive cure for DADA2 with > 95% survival.Peer reviewe

Hematopoietic cell transplantation cures adenosine deaminase 2 deficiency: report on 30 patients

Purpose Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-alpha) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. Methods We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Results Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. Conclusion HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. Clinical Implications HCT is a definitive cure for DADA2 with > 95% survival.Transplantation and immunomodulatio