The increasing potential for accidental radiation exposure from either nuclear accidents or terrorist activities has escalated the need for radiation countermeasure development. We previously showed that a 30-day course of high-dose captopril, an ACE inhibitor, initiated 1–4 h after total body irradiation (TBI), improved Hematopoietic Acute Radiation Syndrome (H-ARS) and increased survival in mice. However, because of the time likely required for the deployment of a stockpiled radiation countermeasure to a radiation mass casualty site, there is a need for therapies that can be administered 24–48 hours after initial exposure. Using C57BL/6 mice exposed to an LD50-80/30 of 60Co TBI (7.75–7.9 Gy, 0.615 Gy/min), we show that low-dose captopril administration, initiated as late as 48 h post-TBI and continued for 14 days, significantly enhanced overall survival similarly to high-dose, rapid administration. Captopril treatment did not affect radiation-induced cell cycle arrest genes or the immediate loss of hematopoietic precursors. Reduced mortality was associated with the recovery of bone marrow cellularity and mature blood cell recovery at 21–30 days post-irradiation. Captopril reduced radiation-induced cytokines EPO, G-CSF, and SAA in the plasma. Finally, delayed captopril administration mitigated brain micro-hemorrhage at 21 days post-irradiation. These data indicate that low dose captopril administered as late as 48 h post-TBI for only two weeks improves survival that is associated with hematopoietic recovery and reduced inflammatory response. These data suggest that captopril may be an ideal countermeasure to mitigate H-ARS following accidental radiation exposure.
Introduction: Cervical carcinoma is an important women’s health problem throughout the world.There are very few published data on this disease in Nepal. We wanted to study the pattern ofcervical carcinoma based on hospital data.Methods: A 10 years retrospective study of scenario of cervical carcinoma was conducted. The datahave been analyzed according to age, occurrence of other cancers, histological type, religion, riskfactors and district wise.Results: The number of cervical carcinoma showed a rising pattern over the 10 year period. Themedian age of the patients was 45 years and maximum frequency (33%) of cases were found in theage group 40 to 49 years. Squamous cell carcinoma comprised 40% of cases, Adenocarcinoma 4% and1.1% cases were of mixed variety. 92% of cases were Hindu by religion. 43% of patients were smokerin our study, 5% had positive family history. Chitwan with 7.35% had the maximum number of casesfollowed by Rupandehi with 6.40% and Nawalparasi with 5.41%.Conclusions: The cancer pattern revealed by the present study provides valuable leads to cervicalcancer epidemiology in Nepal. Routine cytological screening of the population for cervical cancer ishighly necessary for its early detection and treatment.Key Words: Cervical carcinoma, hospital based study, Nepal, pattern
Allogeneic stem cell transplantation is currently the only curative therapy for primary myelofibrosis (MF), while the JAK2 inhibitor, ruxolitinib. Has been approved only for palliation. Other therapies are desperately needed to reverse life‐threatening MF. However, the cell(s) and cytokine(s) that promote MF remain unclear. Several reports have demonstrated that captopril, an inhibitor of angiotensin‐converting enzyme that blocks the production of angiotensin II (Ang II), mitigates fibrosis in heart, lung, skin and kidney. Here, we show that captopril can mitigate the development of MF in the Gata1 low mouse model of primary MF. Gata1 low mice were treated with 79 mg/kg/d captopril in the drinking water from 10 to 12 months of age. At 13 months of age, bone marrows were examined for fibrosis, megakaryocytosis and collagen expression; spleens were examined for megakaryocytosis, splenomegaly and collagen expression. Treatment of Gata1 low mice with captopril in the drinking water was associated with normalization of the bone marrow cellularity; reduced reticulin fibres, splenomegaly and megakaryocytosis; and decreased collagen expression. Our findings suggest that treating with the ACE inhibitors captopril has a significant benefit in overcoming pathological changes associated with MF.
Background: Acid base disorders are common in the ICU patients and pose a great burden in the management of the underlying condition.Methods: Identifying the type of acid-base disorders in ICU patients using arterial blood gas analysis This was a retrospective case-controlled comparative study. 46 patients in intensive care unit of a reputed institution and comparing the type of acid-base disorder amongst infectious (10) and non-infectious (36) diseases.Results: Of the study population, 70% had mixed acid base disorders and 30% had simple type of acid base disorders. It was found that sepsis is associated with mixed type of acid-base disorders with most common being metabolic acidosis with respiratory alkalosis. Non-infectious diseases were mostly associated with metabolic alkalosis with respiratory acidosis. Analysis of individual acid base disorders revealed metabolic acidosis as the most common disturbance.Conclusions: These results projected the probability of acid bases disorders in various conditions and help in the efficient management. Mixed acid base disorders are the most common disturbances in the intensive care setup which is metabolic acidosis with respiratory alkalosis in infectious diseases and metabolic acidosis is the most common simple type of acid base disorder.
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