The role of oxidative stress and neuroinflammatory mediators in the pathogenesis of high-altitude cerebral edema in rats.

High-altitude environments present extreme conditions characterized by low barometric pressure and oxygen deficiency, which can disrupt brain functioning and cause edema formation. The objective of the present study is to investigate several biomolecule expressions and their role in the development of High Altitude Cerebral Edema in a rat model. Specifically, the study focuses on analyzing the changes in total arginase, nitric oxide, and lipid peroxidation (MDA) levels in the brain following acute hypobaric hypoxic exposure (7620 m, SO2=8.1 %, for 24 h) along with the histopathological assessment. The histological examination revealed increased TNF-α activity, and an elevated number of mast cells in the brain, mainly in the hippocampus and cerebral cortex. The research findings demonstrated that acute hypobaric hypoxic causes increased levels of apoptotic cells, shrinkage, and swelling of neurons, accompanied by the formation of protein aggregation in the brain parenchyma. Additionally, the level of nitric oxide and MDA was found to have increased (p<0.0001), however, the level of arginase decreased indicating active lipid peroxidation and redox imbalance in the brain. This study provides insights into the pathogenesis of HACE by evaluating some biomolecules that play a pivotal role in the inflammatory response and the redox landscape in the brain. The findings could have significant implications for understanding the neuronal dysfunction and the pathological mechanisms underlying HACE development.

Morphological abnormalities of peripheral blood cells among patients with COVID-19 disease.

Purpose: The hematological changes in COVID-19 patients continue to receive great attention, especially in the field of public health. To our knowledge, coronavirus disease may be identified based on the severity of illness, and the study of peripheral blood smears may offer important information to facilitate the identification. Thus, we evaluated the morphological abnormalities (atypical and immature lymphocytes, lymphocytes with micronuclei, various nuclear abnormalities among erythrocytes) and quantitative changes in peripheral blood cells among 48 individuals with COVID-19 disease. Methods: The present study is a retrospective analysis of 48 individuals, including 24 hospitalized patients diagnosed with COVID-19 disease. The blood smears of all patients were subjected to a hematological examination to identify various morphological abnormalities in white and red blood cells. In addition, a micronucleus test was conducted to assess the incidence of chromosomal damage in lymphocytes. Furthermore, the complete blood count (CBC) was performed to evaluate changes in peripheral blood cells, particularly the differential total leukocyte count, which could indicate the immune response against viral infection in COVID-19 patients. Results: The findings of the hematological study conducted on patients diagnosed with COVID-19 disease revealed neutrophilia, eosinophilia, mild monocytosis, decreased hematocrit level, elevated erythrocyte sedimentation rate (ESR), and immature leukocytes. It was observed that patients who were infected with coronavirus demonstrated mild thrombocytopenia. Furthermore, the micronucleus test indicated the presence of immature cells with micronuclei among lymphocytes and numerous nuclear abnormalities in red blood cells. These results help to shed light on the hematological changes that occur in COVID-19 patients, and could potentially contribute to the development of more effective treatments for the disease. Conclusions: The examination of complete blood counts (CBCs) in conjunction with peripheral blood smears offers a potential means of identifying the impact of SARS-CoV-2 infection on the hematopoietic and immune systems, thereby providing early indications of inflammation. Based on a study, it has been suggested that SARS-CoV-2 may affect red and white blood cells causing morphological alterations thereby establishing a corresponding relationship with disease severity.

Hypericum alpestre extract exhibits in vitro and in vivo anticancer properties by regulating the cellular antioxidant system and metabolic pathway of L-arginine.

Conventional treatment methods are not effective enough to fight the rapid increase in cancer cases. The interest is increasing in the investigation of herbal sources for the development of new anticancer therapeutics. This study aims to investigate the antitumor capacity of Hypericum alpestre (H. alpestre) extract in vitro and in vivo, either alone or in combination with the inhibitors of the  l-arginine/polyamine/nitric oxide (NO) pathway, and to characterize its active phytochemicals using advanced chromatographic techniques. Our previous reports suggest beneficial effects of the arginase inhibitor NG-hydroxy-nor- l-arginine and NO inhibitor NG-nitro-Larginine methyl ester in the treatment of breast cancer via downregulation of polyamine and NO synthesis. Here, the antitumor properties of H. alpestre and its combinations were explored in vivo, in a rat model of mammary gland carcinogenesis induced by subcutaneous injection of 7,12-dimethylbenz[a]anthracene. The study revealed strong antiradical activity of H. alpestre aerial part extract in chemical (DPPH/ABTS) tests. In the in vitro antioxidant activity test, the H. alpestre extract demonstrated pro-oxidant characteristics in human colorectal (HT29) cells, which were contingent upon the hemostatic condition of the cells. The H. alpestre extract expressed a cytotoxic effect on HT29 and breast cancer (MCF-7) cells measured by the MTT test. According to comet assay results, H. alpestre extract did not exhibit genotoxic activity nor possessed antigenotoxic properties in HT29 cells. Overall, 233 substances have been identified and annotated in H. alpestre extract using the LC-Q-Orbitrap HRMS system. In vivo experiments using rat breast cancer models revealed that the H. alpestre extract activated the antioxidant enzymes in the liver, brain, and tumors. H. alpestre combined with chemotherapeutic agents attenuated cancer-like histological alterations and showed significant reductions in tumor blood vessel area. Thus, either alone or in combination with Nω -OH-nor- l-arginine and Nω -nitro- l-arginine methyl ester, H. alpestre extract exhibits pro- and antioxidant, antiangiogenic, and cytotoxic effects.

Histological and cytochemical analysis of the brain under conditions of hypobaric hypoxia-induced oxygen deficiency in albino rats.

High altitude sickness is a life-threatening disease that occurs among acclimatized individuals working or living at a high altitude accompanied by hypobaric hypoxia exposure. The prolonged influence of hypobaric hypoxia on the brain may trigger neuronal damage and cell death due to an oxygen deficiency. The purpose of the current study was to investigate the histomorphological changes in the hippocampus, cerebral cortex, cerebellar cortex, and striatum of the rat's brain following chronic hypobaric hypoxia. Fourteen albino rats were used for this investigation. The animals were exposed to chronic hypobaric hypoxia in the special decompression chamber at an altitude of 7000 m for 7 days. The histological analysis was conducted via toluidine staining and silver impregnation. DNA damage and cell apoptosis were assessed via Feulgen staining. The histochemical assessment revealed increased dark neurons in the hippocampus with cell swelling. Silver impregnation showed increased argyrophilic neurons in the cerebellar cortex, striatum, CA1 subfield of the hippocampus, and cerebral cortex. The cytochemical analysis determined the increased apoptotic cells with hyperchromatic condensation and pyknosis in the hippocampus subfields and cerebral cortex. In addition, it has been observed that hypoxia has resulted in small hemorrhages and perivascular edema within the cerebellar and cerebral cortex. The results indicate brain injury observed in the various parts of the brain towards hypobaric hypoxia, however, the hippocampus showed greater vulnerability against hypoxic exposure in comparison to the striatum, cerebellum, and cerebral cortex. These changes support our insights regarding brain intolerance under conditions of hypoxia-induced oxygen deficiency and its histomorphological manifestations.

Antihyperglycemic activity of L-norvaline and L-arginine in high-fat diet and streptozotocin-treated male rats.

BACKGROUND: A decrease in nitric oxide (NO) bioavailability has been shown to cause hyperglycemia, type II diabetes mellitus (DM), and chronic cardio-metabolic complications. In turn, hyperglycemia and hypercholesterolemia are associated with increased oxidative stress that leads to reduced nitric oxide bioavailability through disruption of L-arginine transport into cells, inactivation of nitric oxide synthase, and activation of arginase. Upregulation of arginase has been demonstrated in both diabetic patients and animal models of hyperglycemia and type 2 diabetes. L-norvaline is a nonselective inhibitor of arginase that increases NO production and promotes the normal functioning of the vascular endothelium. Another means of increasing NO bioavailability in the cardiovascular system is L-arginine supplementation. Whether L-norvaline and L-arginine have antihyperglycemic effects has not been studied. HYPOTHESIS: We hypothesized that inhibition of arginase will provide an antihyperglycemic effect and, as a result of the recovery of NO bioavailability, will protect against oxidative stress and hypercholesterolemia. METHODS: Rats were fed a high-fat diet (HFD) for three weeks concomitant with the two-time injection of 30 mg/kg of streptozotocin (STZ) to induce stable hyperglycemia. We studied the antihyperglycemic properties of arginase inhibition (via L-norvaline) and its combination with NOS substrate supplementation (via L-arginine). RESULTS: Treatment of HFD/STZ mice with L-norvaline and L-arginine reduced fasting blood glucose levels by 27.1% vs. untreated HFD/STZ rats (p < 0.001). Blood levels of total cholesterol, low-density lipoprotein (LDL), and malondialdehyde (MDA), a marker for oxidative stress, were significantly decreased in both L-norvaline- and L-norvaline+L-arginine-treated HFD/STZ rats when compared with untreated rats. In addition, administration of L-norvaline and L-arginine reversed the progression of pancreatic and kidney pathology in HFD/STZ rats as assessed by histology (p < 0.001). CONCLUSIONS: Both L-norvaline and L-arginine act as potent antihyperglycemic agents and can represent alternative therapeutic tools in individuals with hyperglycemia and pre-diabetes.

The potential therapeutic effect of NG-hydroxy-nor-L-arginine in 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats.

Advances in our understanding of the metabolism and molecular functions of arginine and their alterations in cancer have led to resurgence in the interest of targeting arginine catabolism as an anticancer strategy. Therefore, arginase inhibitors have been proposed as a way to treat cancer. In this study, the anti-tumor potential of the arginase inhibition by NG-hydroxy-nor-L-arginine (nor-NOHA) (3 mg/kg/day, i.p.), administered for 5 weeks (parallel tumors development, every 3th day) against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis in rats has been investigated. Treatment by nor-NOHA has obvious inhibition effects on development of carcinogenesis in rats was shown. That was seen in downregulation of rats' tumors size and number, mortality rate, in stopped alteration of tissue histopathology, in decrease of polyamines, NO and MDA (malondialdeide) concentrations (in blood). Results have shown arginase and NO-synthase can cooperate to restrain quantities of polyamines and NO for cancer progression. The results obtained can serve as a base to use this model for determination of productive, noncytotoxic antitumor and immune modulating concentration of anticancer agents. Perspectives of targeting arginase and NOS in cancer management can ground application in clinical medicine.

Tuberculosis treatment and Smoking, Armenia, 2014-2016.

INTRODUCTION: Tuberculosis and tobacco prove to be increasingly apparent world problems. Armenia is a developing country which is facing issues related to the high rates of tobacco consumption. Moreover, it is among the list of high multi-drug resistant (MDR) Tuberculosis TB burden countries. Treatment success rate in Armenia for sputum smear-positive cases never reached World Health Organization's (WHO) target of 85% in last 15 years. Data from different studies completed across the world suggests that there is an association between smoking and negative treatment outcomes. METHODS: This retrospective study was designed to investigate aforementioned associations between TB treatment outcomes and smoking status of TB patients. Data for the study were derived from the national data available in the electronic database of the Armenian National TB Center. RESULTS: Based on inclusion and exclusion criteria 992 TB patients registered in 2014 were enrolled in this study. All of them are were TB patients in which 387 were smokers and 605 were non-smokers. Notably, adjusted analysis showed that individuals who smoked during TB treatment had 1.61 higher odds of having unsuccessful TB treatment outcome. Additionally, consistent with the literature, statistically significant association was identified between TB treatment outcome and other well factors such as sputum smear status (OR = 2.24, p < 0.01), HIV status (OR, = 1.87, p < 0.01) of patients, etc. CONCLUSIONS: The smoking, HIV positive status, positive sputum smear microscopy test were identified as an important factors associated with the unsuccessful TB treatment outcome in Armenia. It highlights the necessity of having specific restrictions and campaign programs to reduce smoking rates among TB patients in order to improve current TB treatment and care services throughout Armenia.

Summary of notifiable diseases--United States, 2012.

The Summary of notifiable diseases--United States, 2012 contains the official statistics, in tabular and graphic form, for the reported occurrence of nationally notifiable infectious diseases in the United States for 2012. Unless otherwise noted, the data are final totals for 2012 reported as of June 30, 2013. These statistics are collected and compiled from reports sent by state health departments and territories to the National Notifiable Diseases Surveillance System (NNDSS), which is operated by CDC in collaboration with the Council of State and Territorial Epidemiologists (CSTE). The Summary is available at http://www.cdc.gov/mmwr/mmwr_nd/index.html. This site also includes Summary publications from previous years.

Late HIV diagnosis and determinants of progression to AIDS or death after HIV diagnosis among injection drug users, 33 US States, 1996-2004.

BACKGROUND: The timeliness of HIV diagnosis and the initiation of antiretroviral treatment are major determinants of survival for HIV-infected people. Injection drug users (IDUs) are less likely than persons in other transmission categories to seek early HIV counseling, testing, and treatment. Our objective was to estimate the proportion of IDUs with a late HIV diagnosis (AIDS diagnosis within 12 months of HIV diagnosis) and determine the factors associated with disease progression after HIV diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Using data from 33 states with confidential name-based HIV reporting, we determined the proportion of IDUs aged >or=13 years who received a late HIV diagnosis during 1996-2004. We used standardized Kaplan-Meier survival methods to determine differences in time of progression from HIV to AIDS and death, by race/ethnicity, sex, age group, CD4(+) T-cell count, metropolitan residence, and diagnosis year. We compared the survival of IDUs with the survival of persons in other transmission categories. During 1996-2004, 42.2% (11,635) of 27,572 IDUs were diagnosed late. For IDUs, the risk for progression from HIV to AIDS 3 years after HIV diagnosis was greater for nonwhites, males and older persons. Three-year survival after HIV diagnosis was lower for IDU males (87.3%, 95% confidence interval (CI), 87.1-87.4) compared with males exposed through male-to-male sexual contact (91.6%, 95% CI, 91.6-91.7) and males exposed through high-risk heterosexual contact (HRHC) (91.9%, 95% CI, 91.8-91.9). Survival was also lower for IDU females (89.5%, 95% CI, 89.4-89.6) compared to HRHC females (93.3%, 95% CI, 93.3-93.4). CONCLUSIONS/SIGNIFICANCE: A substantial proportion of IDUs living with HIV received their HIV diagnosis late. To improve survival of IDUs, HIV prevention efforts must ensure early access to HIV testing and care, as well as encourage adherence to antiretroviral treatment to slow disease progression.