The state of thrombotic readiness in rats at suprathreshold physical load and its correction by products of velvet antler industry

2018 ◽  
Author(s):  
А.А. Блажко ◽  
И.И. Шахматов ◽  
И.В. Ковалев ◽  
Ю.А. Бондарчук ◽  
О.М. Улитина ◽  
...  
Keyword(s):  
Reproductive Organs ◽  
Physical Load ◽  
Internal Organs ◽  
Group 4 ◽  
Partial Activation ◽  
Velvet Antler ◽  
Male Wistar Rats ◽  
Body Resistance ◽  
Group 3

Введение. При действии чрезмерных стрессоров различной природы система гемостаза может отвечать формированием состояния тромботической готовности, а чтобы избежать его развития необходимо повышать устойчивость организма и, в частности, системы гемостаза к стрессорным воздействиям. Одним из способов является применение продуктов пантового оленеводства. Цель исследования: оценить состояние системы гемостаза у крыс при однократной сверхпороговой физической нагрузке разной продолжительности, а также определить адаптационную роль предварительного курсового приема концентрата, содержащего кровь и гистолизат из репродуктивных органов марала. Материалы и методы. Исследования выполнены на 50 крысах-самцах линии Wistar: 4 экспериментальные группы и группа интактных животных по 10 крыс. Животных групп 1 и 2 подвергали 4-часовой и 8-часовой физической нагрузке, соответственно. Животные группы 3 принимали продукты пантового оленеводства (концентрат) в течение 30 дней и на 31-й день подвергались 8-часовой физической нагрузке. Животные группы 4 принимали концентрат в течение 30 дней и не подвергались воздействию физической нагрузки. Интактные крысы принимали воду в том же объеме, что и экспериментальные животные, и не подвергались воздействию физической нагрузки. Состояние системы гемостаза оценивали методом тромбоэластографии. Проведено гистологическое исследование легких крыс во всех группах. Результаты. 4-часовая физическая нагрузка вызывала частичную активацию системы гемостаза у крыс, усиливая наступление фазы инициации свертывания крови. 8-часовая физическая нагрузка вызывала у крыс развитие состояния тромботической готовности. Заключение. Предварительный курсовой прием продуктов пантового оленеводства снижал риск развития состояния тромботической готовности и повреждения внутренних органов у крыс после сверхпороговой физической нагрузки за счет повышения фибринолитической активности плазмы крови. Introduction. Under the action of excessive stressors of diff erent nature, hemostasis can respond by forming a state of thrombotic readiness. In order to avoid its development, it is necessary to increase body resistance and hemostasis in particular to stress eff ects. One of the methods is the usage of the products of velvet antler industry. Aim: to assess hemostasis in rats at a single suprathreshold physical load of different duration and to determine the adaptive role of preliminary intake of a concentrate containing blood and histolysate from maral reproductive organs. Materials and methods. Studies were performed on 50 male Wistar rats: 4 experimental groups and a group of intact animals, 10 rats each. Animals of groups 1 and 2 were exposed to 4-hour and 8-hour physical load, respectively. Animals of group 3 received products of velvet antler industry (concentrate) for 30 days and on 31st day were exposed to 8-hour suprathreshold physical load. Animals of group 4 received a concentrate for 30 days and were not exposed to physical stress. Intact rats took water in the same volume as experimental animals and were not exposed to physical activity. Hemostasis was assessed by thromboelastography. Histological examination of lungs was carried out in rats from all groups. Results. The 4-hour physical load caused partial activation of hemostasis, enhancing the phase onset of blood coagulation. The 8-hour physical load caused the development of thrombotic readiness. Conclusion. Preliminary intake of velvet antler products reduced the risk of thrombotic readiness development and damage of internal organs in rats after suprathreshold physical load due to increasing of blood fibrinolytic activity.

scholarly journals Effects of splenic allograft in lipid profile of non-splenectomized rats: the immune and metabolic role of the "double spleen"

2014 ◽  
Vol 41 (2) ◽  
pp. 122-127 ◽  
Author(s):  
Thiago Barbosa Gonçalves ◽  
Vitor Nagai Yamaki ◽  
Daniel Haber Feijó ◽  
Luis Eduardo Almeida de Souza ◽  
Edvaldo Silveira ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Total Cholesterol ◽  
Splenic Tissue ◽  
Control Group ◽  
Group 4 ◽  
Metabolic Role ◽  
Male Wistar Rats ◽  
Group 3 ◽  
Group 1

OBJECTIVE: To elucidate the role of the spleen and splenic allograft in lipid control and evaluate its effect on the lipid profile of rats.METHOD: 32 male Wistar rats were randomly assigned into four groups: control group (1), total splenectomy group (2), splenectomy and implantation of allograft group (3) and double spleen group (4). Each group was subdivided into two subgroups: A and B, based on the death of the animals after 30 or 120 days of monitoring. The procedures in groups 2, 3 and 4 were made simultaneously, and splenectomized animals, groups 2 and 3 were donors, respectively, for the animals of groups 3 and 4. In group 4 the spleen was preserved and the animals received implants from the spleens of rats from group 3. The regeneration of splenic tissue was evaluated by macroscopic and microscopic analyzes of the grafts and own spleens, as well as with measurements of VLDL, HDL, LDL, total cholesterol and triglycerides.RESULTS: after 120 days, Group 4 showed levels of total cholesterol and LDL lower than the other groups. Group 1 had higher levels of lipids.CONCLUSION: The technique of double spleen was effective in the control of lipid metabolism, corroborating the function of the spleen as a reserve of lipids.

scholarly journals Prevention of microcirculatory disorders in rats on suprathreshold physical exertion using the products of velvet antler industry

2018 ◽  
Vol 99 (6) ◽  
pp. 942-946
Author(s):  
A A Blazhko ◽  
I I Shakhmatov ◽  
V I Kiselev ◽  
I V Kovalev
Keyword(s):  
Blood Flow ◽  
Physical Exertion ◽  
Reproductive Organs ◽  
Physical Load ◽  
Doppler Flowmetry ◽  
Experimental Animals ◽  
Intact Group ◽  
Velvet Antler ◽  
Male Wistar Rats ◽  
Experimental Group

Aim. To assess the microcirculatory bloodstream after suprathreshold physical load in rats with preceding intake of products of velvet antler industry, as well as to determine which microcirculatory reactions cause the adaptive effect. Methods. The study included 30 male Wistar rats. Two groups of experimental animals received the concentrate containing blood and histolysate of Siberian stag reproductive organs, 4.5 ml per day. The rats of the first experimental group were subjected to an 8-hour physical load on day 31, and rats of the second group were not subjected to the load. Indices of microcirculation obtained by laser Doppler flowmetry in experimental animals were compared to those of intact rats. Results. In animals of the first experimental group, the amplitude of respiratory waves increased in comparison with intact animals, while the remaining indices of the microcirculation system did not differ from those of the intact group. In the rats of the second experimental group, there was an increase in the flax, which indicates an increase in the modulation of the blood flow; in rats an increase in the amplitude of endothelial and vasomotor waves was revealed in comparison with intact animals against the background of constant amplitudes of respiratory and pulse waves. Conclusion. Preceding 30-day intake of a concentrate containing blood and histolysate of Siberian stag reproductive organs, in general, was found to prevent the development of disturbances of the microcirculatory bloodstream in rats after the suprathreshold physical load due to active mechanisms of blood flow regulation - increase of the amplitudes of endothelial and vasomotor waves.

TMOD-26. MYC OVEREXPRESSION AND SMARCA4 LOSS IN GRANULE CELL PRECURSORS COOPERATE TO DRIVE MEDULLOBLASTOMA FORMATION IN MICE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi221-vi221
Author(s):  
Carolin Göbel ◽  
Dörthe Holdhof ◽  
Melanie Schoof ◽  
Catena Kresbach ◽  
Ulrich Schüller
Keyword(s):  
Granule Cell ◽  
Clinical Course ◽  
Tumor Development ◽  
Tumor Formation ◽  
Human Group ◽  
Group 4 ◽  
Small Cohort ◽  
Group 3 ◽  
Granule Cell Precursors

Abstract Mutations in SMARCA4 are frequently identified in medulloblastoma, the most common pediatric malignant brain tumor. However, the functional significance of these mutations and their suitability as a therapeutic target remain largely unclear. Medulloblastomas are divided into 4 subgroups according to their localization, molecular biology, and clinical course: WNT, SHH, Group 3, and Group 4. Group 3 medulloblastomas are associated with the poorest outcome and frequently show amplifications of the oncogene MYC. Additionally, SMARCA4 is mutated in around 15 % of cases. The few mouse models developed for this entity so far all involve the overexpression of MYC, mostly in combination with other drivers. However, none of these models include alterations in Smarca4. In our approach, we combined an overexpression of MYC with a loss of SMARCA4 in granule cell precursors, which successfully induced tumor formation in mice. For this purpose, granule cell precursors were isolated from 7-day-old Math1-creER T2 ::Smarca4 fl/fl pups after tamoxifen induced loss of SMARCA4. MYC overexpression was achieved by lentiviral transduction and transduced cells were transplanted into immunodeficient CD1 nu/nu mice. Preliminary results within a small cohort showed tumor formation in 5/19 transplanted mice (26 %) after 6 months. Immunohistochemically, tumors all stained negative for SMARCA4. In a next step, additional cohorts will elucidate if tumor development is indeed accelerated by or even dependent on the loss of SMARCA4. Additionally, the neoplastic potential of tumor cells will be verified with the aid of secondary recipient mice. To evaluate to what extent the generated tumors are comparable to human Group 3 medulloblastomas, tumors will be extensively analyzed on a morphological, transcriptional, and epigenetic level. Altogether, we hope to establish a suitable mouse model for SMARCA4 mutated Group 3 medulloblastoma that will help to elucidate the role of SMARCA4 in tumor development and to identify new therapeutic targets.

P5392Epicardium derived cells promote sympathetic ganglionic outgrowth towards myocardium in vitro

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Ge ◽  
A M Smits ◽  
J C Van Munsteren ◽  
T Van Herwaarden ◽  
A M D Vegh ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Autonomic Innervation ◽  
Cardiac Damage ◽  
Group 4 ◽  
Group 3 ◽  
Cervical Ganglia ◽  
Group 2 ◽  
Group 1

Abstract Background The autonomic nerve system is essential to maintain homeostasis in the body. In the heart, autonomic innervation is important for adjusting the physiology to the continuously changing demands such as stress responses. After cardiac damage, excessive neurite outgrowth, referred to as autonomic hyperinnervation, can occur which is related to ventricular arrhythmias and sudden cardiac death. The cellular basis for this hyperinnervation is as yet unresolved. Here we hypothesize a role for epicardium derived cells (EPDCs) in stimulating sympathetic neurite outgrowth. Purpose To investigate the potential role of adult EPDCs in promoting sympathetic ganglionic outgrowth towards adult myocardium. Method Fetal murine superior cervical ganglia were dissected and co-cultured with activated adult mesenchymal epicardium-derived cells (EPDCs) or/and adult myocardium in a 3D collagen gel culture system. Four experiment groups were included: Group 1: Vehicle cultures (ganglia cultured without EPDC/myocardium) (n=48); Group 2: ganglia co-cultured with EPDCs (n=38); Group 3: ganglia co-cultured with myocardium (n=95); and group 4: ganglia co-cultured with both EPDCs and myocardium (n=96). The occurrence of neurite outgrowth was assessed in each group. The density of neurites that showed directional sprouting (i.e. sprouting towards myocardium) was assessed as well with a semi-automatic quantification method. Finally, sub-analyses were made by taking gender into account. Results Cervical ganglia cultured with EPDCs alone (group 2) showed increased neurite outgrowth compared to vehicle cultures (group 1), however the neurites did not show directional sprouting towards EPDCs. When co-cultured with myocardium (group 3), directional neurite outgrowth towards myocardium was observed. Compared to the ganglia-myocardium co-cultures, directional outgrowth was significantly increased in co-cultures combining myocardium and EPDCs (group 4), and the neurite density was also significantly augmented. Comparison between males and female ganglia demonstrated that more neurite outgrowth occurred in female-derived ganglia than in male-derived ganglia under the same co-culture conditions. Conclusion Activated adult EPDCs promote sympathetic ganglionic outgrowth in vitro. Sex differences exist in the response of ganglia to EPDCs, and female-derived ganglia appear more sensitive to EPDC-signalling. Results support a role of EPDCs in cardiac autonomic innervation and open avenues for exploring of their role in ventricular hyperinnervation after cardiac damage.

Experimental model of posttraumatic syringomyelia: the role of adhesive arachnoiditis in syrinx formation

1994 ◽  
Vol 80 (1) ◽  
pp. 133-139 ◽  
Author(s):  
Ki Hong Cho ◽  
Yoshinobu Iwasaki ◽  
Hiroyuki Imamura ◽  
Kazutoshi Hida ◽  
Hiroshi Abe
Keyword(s):  
Normal Saline ◽  
Subarachnoid Space ◽  
Saline Solution ◽  
Traumatic Injury ◽  
Content Type ◽  
Group 4 ◽  
Kaolin Injection ◽  
Group 3 ◽  
Group 2

✓ An experimental model was devised to elucidate the role of spinal blockade in posttraumatic syringomyelia. Thirty-eight Japanese White rabbits, each weighing about 3 kg, were used in this study. The animals were divided into four groups: in Group 1, eight animals received traumatic injury only; in Group 2, 12 animals received traumatic injury following injection of 100 mg kaolin suspended in 1 cc normal saline solution into the subarachnoid space at the site of trauma; in Group 3, nine animals received traumatic injury following injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid space at the site of trauma; and in Group 4, nine animals without traumatic injury received an injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid space. The subjective criteria for syrinx formation were the presence of a definite round cyst having a smooth margin and an upper or lower extension of more than 2 cm from the injured site. Syrinx formation was seen in 12.5% (one of eight rabbits) in Group 1, 41.7% (five of 12 animals) in Group 2, 55.5% (five of nine rabbits) in Group 3 and 0% (none of nine animals) in Group 4 (p < 0.05). There was a tendency for the combined trauma/kaolin injection groups to be more prone to develop a syrinx. In the kaolin injection only group (Group 4), no animal showed a definite cyst or an extending cavity during the experimental period. The results suggest that kaolin enhances the extension of multiple small cavities that have already formed at the time of initial injury. The difference between the frequency of syrinx formation and the time of survival was statistically significant well beyond the 0.05% level. The overall difference, relating to the frequency of syrinx development, group, and duration of survival, was also statistically significant. In summary, subarachnoid block secondary to adhesive arachnoiditis is important in initiating the extension of the syringomyelia cavity.

scholarly journals Preclinical Models of Craniospinal Irradiation for Medulloblastoma

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 133 ◽  
Author(s):  
Jennifer L. Stripay ◽  
Thomas E. Merchant ◽  
Martine F. Roussel ◽  
Christopher L. Tinkle
Keyword(s):  
Small Animal ◽  
Craniospinal Irradiation ◽  
Tumor Control ◽  
Preclinical Models ◽  
Treatment Interventions ◽  
Leptomeningeal Seeding ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Group 3

Medulloblastoma is an embryonal tumor that shows a predilection for distant metastatic spread and leptomeningeal seeding. For most patients, optimal management of medulloblastoma includes maximum safe resection followed by adjuvant craniospinal irradiation (CSI) and chemotherapy. Although CSI is crucial in treating medulloblastoma, the realization that medulloblastoma is a heterogeneous disease comprising four distinct molecular subgroups (wingless [WNT], sonic hedgehog [SHH], Group 3 [G3], and Group 4 [G4]) with distinct clinical characteristics and prognoses has refocused efforts to better define the optimal role of CSI within and across disease subgroups. The ability to deliver clinically relevant CSI to preclinical models of medulloblastoma offers the potential to study radiation dose and volume effects on tumor control and toxicity in these subgroups and to identify subgroup-specific combination adjuvant therapies. Recent efforts have employed commercial image-guided small animal irradiation systems as well as custom approaches to deliver accurate and reproducible fractionated CSI in various preclinical models of medulloblastoma. Here, we provide an overview of the current clinical indications for, and technical aspects of, irradiation of pediatric medulloblastoma. We then review the current literature on preclinical modeling of and treatment interventions for medulloblastoma and conclude with a summary of challenges in the field of preclinical modeling of CSI for the treatment of leptomeningeal seeding tumors.

scholarly journals Evaluation of protective effect of myricetin, a bioflavonoid in dimethyl benzanthracene-induced breast cancer in female Wistar rats

2014 ◽  
Vol 03 (02) ◽  
pp. 107-111 ◽  
Author(s):  
J. K. Jayakumar ◽  
P. Nirmala ◽  
B.A. Praveen Kumar ◽  
Ashok P. Kumar
Keyword(s):  
Breast Cancer ◽  
Wistar Rats ◽  
Statistical Significance ◽  
Treated Animal ◽  
Group 4 ◽  
Female Wistar Rats ◽  
Group 3 ◽  
Group 2 ◽  
And Control

Abstract Background: Breast cancer is one of the most common cancers worldwide. Alarmingly, the incidence of breast cancer is rising rapidly in India. Aim: The present research was focused to assess the role of myricetin; a bioflavonoid in 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer in female Wistar rats. Materials and Methods: A total of 36 female Wistar rats (total 6 groups, n = 6 per group) 6 - 8 weeks old, weighing 150 gm were used in the study. DMBA was given at the dose of 7.5 mg/kg subcutaneously in the mammary region once a week for 4 consecutive weeks in group 2. Vincristine was given in the dose of 500 μg/kg intraperitonially every week for 4 consecutive weeks in group 3. Myricetin was given orally in a dose of 50, 100, and 200 mg/kg in group 4, 5, and 6 respectively. The statistical significance of the data was determined using one way analysis of variance and Duncan’s multiple range test. Results: The result showed that myricetin increased the antioxidant levels in plasma, erythrocyte lysate, and breast tissue and was effective in preventing the oxidative damage induced by the carcinogen DMBA. Myricetin 50, 100, and 200 mg/kg/oral for 120 days treated animal resulted comparable results to that of standard vincristine and control groups. Conclusions: Myricetin was found to be either equieffective or more effective than vincristine in all the parameters studied. Myricetin proved the capacity of flavonols to act as antioxidant in cells represents a potential treatment in the field of oncology.

scholarly journals Ganoderma Lucidum from Red Mushroom Attenuates Formaldehyde-Induced Liver Damage in Experimental Male Rat Model

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 313
Author(s):  
Babatunde Oluwafemi Adetuyi ◽  
Tolulope Olamide Okeowo ◽  
Oluwatosin Adefunke Adetuyi ◽  
Oluwaseun Abraham Adebisi ◽  
Olubanke Olujoke Ogunlana ◽  
...  
Keyword(s):  
Ganoderma Lucidum ◽  
Ethanol Extract ◽  
Male Rats ◽  
Male Rat ◽  
Protective Potential ◽  
Group 4 ◽  
Male Wistar Rats ◽  
Group 3 ◽  
Group 2 ◽  
Mediated Reduction

The majority of liver-related illnesses are caused by occupational and domestic exposure to toxic chemicals like formaldehyde (FA), which is widely common in Africa and the world at large. Hence, measures should be taken to protect humans from its hazardous effects. This study, therefore, examines the protective potential of Ganoderma lucidum (100 mg/kg body weight) on formaldehyde-induced (40%) liver oxido-inflammation in male rats. Male Wistar rats, 150–200 g, were allotted into four groups of 10 animals as follows: Group 1 was orally treated with 1 mg/mL distilled water, Group 2 was exposed to a 40% formaldehyde vapor environment for 30 min per day, Group 3 was orally treated with 100 mg/kg ethanol extract of Ganoderma lucidum, and Group 4 was co-administered formaldehyde and 100 mg/kg ethanol extract of Ganoderma lucidum. Rats were then sacrificed 24 h after administering the last dose of treatment, and the livers were excised. Ganoderma lucidum significantly reversed the formaldehyde-mediated reduction in body and organ weight. Ganoderma lucidum administration significantly prevented oxido-inflammation by reducing the levels of hydrogen peroxide and malondialdehyde and increasing the activity of antioxidant enzymes and glutathione contents, as well as the normal level of nitrite and myeloperoxidase production in FA-treated rats. Additionally, Ganoderma lucidum reversed a large decline in proinflammatory markers in formaldehyde. Furthermore, Ganoderma lucidum restores formaldehyde-induced histological alterations in the liver. Collectively, our results provide valuable information on the protective potential of Ganoderma lucidum in protecting formaldehyde-induced liver oxido-inflammation in male rats.

Bacteriophages of Clostridium botulinum

1972 ◽  
Vol 18 (1) ◽  
pp. 67-76 ◽  
Author(s):  
C. E. Dolman ◽  
Eva Chang
Keyword(s):  
Clostridium Botulinum ◽  
Phage Type ◽  
Phage Group ◽  
Flexible Tail ◽  
Group 4 ◽  
Group 3 ◽  
Type C ◽  
Group 2 ◽  
Group 1

Temperate bacteriophages of diverse morphology were demonstrated by electron microscopy in toxigenic cultures of Clostridium botulinum. The 41 strains examined included 23 type E and multiple representatives of all other types. Cultures induced with mitomycin-C generally gave better yields, but phages were also demonstrable in untreated cultures.A provisional grouping of toxigenic types into four categories is suggested, based mainly upon associated phage patterns. Group 1 comprises types A, B, and F (all proteolytic), many of whose cultures showed an icosahedral contractile phage; others contained a "bullrushy" phage with elongated head and long flexible tail; some strains yielded both. Group 2, types B and F (non-proteolytic), were associated with icosahedral contractile phages; the latter also had an octahedral flexible phage. Group 3, types C and D, yielded conspicuously large phages with octahedral heads and very long sheathed tails. One type C strain produced a long-tailed icosahedral phage. Type E phages constituted group 4. These were icosahedral with tails generally contracted but sometimes flexible, often accompanied by superfluous sheathed tail-like structures resembling certain bacteriocins. Although non-toxigenic "OS" mutants of types A, B, E, and F were phageless, two non-toxic type E strains yielded phages. The possible role of lysogeny in the toxigenicity of certain types of this species is likely to prove difficult to elucidate.

scholarly journals Seminal Plasma Induces Ovulation in Llamas in the Absence of a Copulatory Stimulus: Role of Nerve Growth Factor as an Ovulation-Inducing Factor

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3224-3232 ◽  
Author(s):  
Marco A. Berland ◽  
Cesar Ulloa-Leal ◽  
Miguel Barría ◽  
Hollis Wright ◽  
Gregory A. Dissen ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Seminal Plasma ◽  
Neural Signals ◽  
Intact Male ◽  
Nerve Growth ◽  
Group 4 ◽  
Group 3 ◽  
Group 2

Llamas are considered to be reflex ovulators. However, semen from these animals is reported to be rich in ovulation-inducing factor(s), one of which has been identified as nerve growth factor (NGF). These findings suggest that ovulation in llamas may be elicited by chemical signals contained in semen instead of being mediated by neural signals. The present study examines this notion. Llamas displaying a preovulatory follicle were assigned to four groups: group 1 received an intrauterine infusion (IUI) of PBS; group 2 received an IUI of seminal plasma; group 3 was mated to a male whose urethra had been surgically diverted (urethrostomized male); and group 4 was mated to an intact male. Ovulation (detected by ultrasonography) occurred only in llamas mated to an intact male or given an IUI of seminal plasma and was preceded by a surge in plasma LH levels initiated within an hour after coitus or IUI. In both ovulatory groups, circulating β-NGF levels increased within 15 minutes after treatment, reaching values that were greater and more sustained in llamas mated with an intact male. These results demonstrate that llamas can be induced to ovulate by seminal plasma in the absence of copulation and that copulation alone cannot elicit ovulation in the absence of seminal plasma. In addition, our results implicate β-NGF as an important mediator of seminal plasma-induced ovulation in llamas because ovulation does not occur if β-NGF levels do not increase in the bloodstream, a change that occurs promptly after copulation with an intact male or IUI of seminal plasma.

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