Prophylactic and Therapeutic Effects of Oleuropein on Reperfusion-Induced Arrhythmia in Anesthetized Rat

Background:

This study was conducted to reveal that whether i.v. injection of oleuropein, the most potent polyphenolic antioxidant in olive leaf, has any effect on the magnitude of reperfusion arrhythmia in anesthetized rats or not.

Methods:

Eighty male Wistar rats were divided into 8 groups of 10 each: groups 1 and 5 were assigned as the prophylactic and treatment control groups, groups 2 and 6 as the prophylactic and treatment groups with lidocaine (10 mg/kg), groups 3 and 4 as the prophylactic groups with 10 and 50 mg/kg oleuropein (i.v.), and groups 7 and 8 as the treatment groups with 10 and 50 mg/kg oleuropein (i.v.), respectively. Reperfusion injury was induced by 5-min regional ischemia and 15-min reperfusion of left anterior descending coronary artery. Heart rate, blood pressure, and electrocardiogram were monitored throughout the procedure.

Results:

blood pressure was significantly decreased by infusion of 50 mg/kg oleuropein in groups 4 and 8, but unlike the lidocaine as a standard anti-arrhythmic drug in groups 2 and 5 had not significant effect on heart rate. The onset of arrhythmia in groups received oleuropein (groups 3, 4, 7, and 8) was significantly delayed. The mortality rate due to irreversible ventricular fibrillation was also significantly reduced in groups 3, 4, 7, and 8. The effect of lidocaine in groups 2 and 5 was more potent than that in oleuropein group.

Conclusion:

These findings indicate that i.v. injection of oleuropein possibly through its antioxidant activity reduces the magnitude of reperfusion-induced arrhythmia.Key Words: Oleuropein, Arrhythmia, Reperfusion, Rats     

Protective Effect of Vitamin E against Diabetes-Induced Oxidized LDL and Aorta Cell Wall Proliferation in Rat

Background:

Hyperlipidemia and oxidized-low-density lipoproteins (Ox-LDL) are important independent cardiovascular risk factors that have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. The purpose of the present study was to investigate the effect of vitamin E on Ox-LDL, lipid profile, C-reactive protein (CRP), and VSMC proliferation of rat aorta.

Methods:

Male Wistar rats (n = 32) were divided into four groups namely: sham (SH), control (C), non-treated diabetic, and vitamin E-treated diabetic (VETD) groups. Ox-LDL, lipid profile, CRP and VSMC proliferation of aorta were measured after 42 days.

Results:

The results revealed that along with a significant increase in VSMC proliferation, the amount of CRP, Ox-LDL, and lipid profiles in diabetic rats. VSMC proliferation was significantly ameliorated, and elevated CRP, Ox-LDL, and lipid profiles were also restored to those of shams in VETD.

Conclusions:

These findings strongly support the idea that diabetes induces Ox-LDL-mediated oxidative stress and VSMC proliferation in aorta of rat and imply that vitamin E has a strong protective effect as an antioxidant. Key Words: Ox-LDL, Vitamin E, Diabetes, VSMC proliferation     

Antioxidant Role of Oleuropein on Midbrain and Dopaminergic Neurons of Substantia Nigra in Aged Rats

Background: Oleuropein is a phenolic compound which is present in the olive leaf extract. The purpose of the present study was to investigate the neuroprotective effect of oleuropein as an antioxidant agent on the substantia nigra in aged rats. Methods: Twenty 18-month-old Wistar rats (450-550 g) were randomly divided into control and experimental groups. The experimental group received a daily single dose of 50 mg/kg of oleuropein by oral gavage for 6 months. The control group received only distilled water. All rats were sacrificed two hours after the last gavage and the brains were removed and midbrains were cut. One part of the midbrains were homogenized and centrifuged. The tissue supernatant was assayed for lipid peroxidation (LPO) and antioxidant enzyme activities. The other part of midbrains fixed and embedded in paraffin, then processed for Nissl and immunohistochemistry (IHC) staining. Data was analyzed using SPSS by t-test. Differences were considered significant for P<0.05. Results: The level of LPO in midbrain of the rats was decreased significantly in the experimental group, but superoxide dismutase, catalase and glutathione peroxidase activities were increased in experimental group compared to control group (P<0.05). Morphometric analyses showed significantly that the experimental group had more neurons in substantia nigra pars compacta (SNc) either in Nissl or IHC staining when compared to control (P<0.05). Conclusion: The results of the present study indicate that treatment of the old rats with oleuropein reduces the oxidative damage in SNc by increasing the antioxidant enzyme activities. Key Words: Oleuropein, Aging, Dopaminergic neurons, Substantia nigra     

Effects of Atorvastatin on the Hypertension-Induced Oxidative Stress in the Rat Brain

Background: It is well known that the development of brain oxidative stress is one of the most serious complications of arterial hypertension that evokes brain tissue damage. The aim of this study was to examine the effects of atorvastatin treatment (20 mg/kg/day), as an antioxidant, to prevent the brain tissue oxidative stress in the hypertensive (HTN) rats. Methods: Experiments were performed in four groups of rats (n = 5 each group): sham, sham-treated, HTN and HTN treated. Rats were made HTN by aortic constriction above the renal arteries. After 30 days, rats were slaughtered under deep anesthesia to remove brain hemispheres. After tissue homogenization, enzyme activities of superoxide dismutase (SOD) and catalase (CAT), as well as glutathione (GSH) content and malondialdehyde (MDA) level were determined by biochemical methods. Results: In HTN rats, arterial blood pressure was increased about 40% and brain enzyme activities of SOD and CAT were significantly decreased compared with sham group. Induction of hypertension significantly decreased GSH content and increased MDA level of brain tissue. Treatment with atorvastatin enhanced the activity of SOD and prevented from GSH decrement during hypertension. Conclusion: Based on the findings of this study, treatment with atorvastatin might have saved the brain tissue of HTN rats from hypertension-induced oxidative stress. Key Words: Atorvastatin, Aortic coarctation, Oxidative stress, Hypertension     

茶多酚对脑损伤保护作用的研究进展

本文根据茶多酚防治帕金森症研究的最新研究成果,并结合茶多酚对脑皮层线粒体、多巴胺神经元的保护作用及对脑代谢相关通路的调控等方面的研究,综述了茶多酚对脑损伤的保护作用.     

Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation

Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm²), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation.     

The Effects of Estrogen Receptors' Antagonist on Brain Edema,Intracranial Pressure and Neurological Outcomes after Traumatic Brain Injury in Rat

Background:

In previous studies, the neuroprotective effect of 17β-estradiol in diffuse traumatic brain injury has been shown. This study used ICI 182,780, a non-selective estrogen receptor antagonist, to test the hypothesis that the neuroprotective effect of 17β-estradiol in traumatic brain injury is mediated by the estrogen receptors.

Methods:

The ovariectomized rats were divided into eight groups. Brain injury was induced by Marmarou’s method. Estrogen was injected 30 minutes after traumatic brain injury, and ICI 182,780 was injected before traumatic brain injury and also before estrogen treatment. In one group only ICI 182,780 was injected. The brain water content and Evans blue dye content were measured 24 and 5 hours after traumatic brain injury, respectively. The neurologic outcomes and intracranial pressure were assessed before, 4, and 24 hours after traumatic brain injury.

Results:

Brain water content and Evans blue content were less in estrogen-treated group comparison to vehicle group. ICI 182,780 eliminated the effects of estrogen on brain edema and brain blood barrier permeability. Intracranial pressure was increased significantly after trauma, and estrogen decreased intracranial pressure at 4 and 24 hours after traumatic brain injury in comparison to vehicle. This inhibitory effect was also eliminated by treatment with ICI182,780. ICI 182,780 also inhibited the estrogen induced increase in neurologic outcomes following traumatic brain injury. However, the use of ICI 182,780 alone had no neuroprotective effect after traumatic brain injury.

Conclusion:

The results suggest that classical estrogen receptors have probably a role in the neuroprotective function of estrogen following traumatic brain injury.Key Words: Estrogens, Intracranial pressure (ICP), Brain edema     

Protective Role of Three Vegetable Peels in Alloxan Induced Diabetes Mellitus in Male Mice

The hitherto unknown glucose regulating role of three vegetable peels from cucurbitaceae family was evaluated. In a preliminary study, effects of ethanolic extracts of Cucurbita pepo, Cucumis sativus and Praecitrullus fistulosus peels were studied at 250 and 500 mg kg⁻¹ d⁻¹ for 15 days in the alterations in serum glucose and in hepatic lipid peroxidation (LPO) in male mice. In the pilot experiment, the effective and safe concentration of each peel was administered (p.o.) for 10 consecutive days and then on 11th and 12th days alloxan was administered along with peel extracts. The treatment was continued up to 15th day. At the end, alterations in serum glucose, insulin, triiodothyronine, thyroxine, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein, hepatic lipid peroxidation, superoxide dismutase and catalase were studied. All the three peel extracts nearly reversed most of these changes induced by alloxan suggesting their possible role in ameliorating diabetes mellitus and related changes in serum lipids. However, Cucurbita pepo peel was found to be the most effective. Total polyphenols, flavonoids and ascorbic acid contents of the test peels were also estimated, which appear to be associated with the observed antidiabetic and antioxidative potentials.     

Neural Protective Effects of Millet and Millet Polyphenols on High-Fat Diet-Induced Oxidative Stress in the Brain

Plant Foods for Human Nutrition - A high fat diet (HFD) is considered to be a risk factor for the development of dementia because it increases oxidative stress in the brain; thus, diets rich in...     

Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats

Background. The major side effect of cisplatin, used in some tumours, is nephrotoxicity. Reactive oxygen species and oxidative damage are the most important factors in cisplatin-induced acute renal failure. The main purpose of this study is to investigate the protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rat. Methods. In this study, animals were randomly divided into 5 groups (6 each). Group one received normal saline (2 ml/day, i.p.). Group two received a single dose of cisplatin (5 mg/kg, i.p.). Groups 3 to 5 received crocin (100, 200 and 400 mg/kg, i.p., respectively, for 4 consecutive days one hour before a single dose of cisplatin (5 mg/kg) only at the first day. Blood samples were taken out (on the fifth day) for measuring the level of urea and creatinine. The kidneys were removed for histopathological and biochemical examinations. Furthermore, 24-hour urinary factors were measured. Results. Blood urea, creatinine and urinary glucose and protein concentrations in crocin-treated groups were significantly lower than those of cisplatin-treated group in a dose-dependent manner. Histopathological studies showed a massive damage in S3 segment of proximal tubules in cisplatin-treated group. No damage was observed in crocin-treated groups. Crocin treatment resulted in a significant and dose-dependent reduction in malondialdehyde concentration as compared to the cisplatin-treated group. Moreover, crocin produced a significant elevation in total thiol and glutathione peroxidase concentrations, as compared with cisplatin-treated group. Conclusion. The results of the present study suggest that crocin has a protective effect against cisplatin-induced acute renal failure and relative oxidative stress.     

Role of GABAB Receptor and L-Arg in GABA-Induced Vasorelaxation in Non-diabetic and Streptozotocin-Induced Diabetic Rat Vessels

Background:

Hypertension is considered an independent risk factor for cardiovascular mortality in diabetic patients. The present study was designed to determine the role of gamma amino butyric acid B (GABA_B) receptor and L-arginine (L-Arg) in GABA-induced vasorelaxation in normal and streptozotocin-induced diabetic rat vessels.

Methods:

Diabetes was induced by a single i.p. injection of streptozotocin (STZ, 60 mg/kg). Eight weeks later, superior mesenteric arteries of all groups were isolated and perfused according to the McGregor method.

Results:

Baseline perfusion pressure of STZ diabetic rats was significantly higher than non-diabetic rats in both intact and denuded endothelium. In the presence of faclofen, a selective GABA_B receptor blocker, GABA-induced relaxation in intact and denuded endothelium mesenteric beds of STZ diabetic rats was suppressed, but this response in non-diabetic rats was not suppressed. Our results showed that in the presence of L-Arg, a nitric oxide precursor, GABA induced vasorelaxation in both diabetic and non-diabetic vessels.

Conclusion:

From the results of this study, it may be concluded that the vasorelaxatory effect of GABA in diabetic vessel is mediated by the GABA_B receptor and nitric oxide, but it seems that in non-diabetic vessel GABA_B receptor does not play any role in GABA-induced vasorelaxation, but nitric oxide induced GABA relaxation in non-diabetic vessel. Key Words: Gamma amino butyric acid (GABA), Diabetes, GABA_B receptor     

人参皂苷Rb3及Rb2组合物对大鼠实验性心肌梗死的保护作用

目的研究人参皂苷Rb,及Rb,组合物对大鼠急性心肌梗死的保护作用。方法采用大鼠结扎左冠状动脉前降支制备急性心肌梗死模型,计算急性心肌梗死24h后的心肌梗死面积（MIS）,测定血清肌酸磷酸激酶（CK）、乳酸脱氢酶（LDH）、天门冬氨酸氨基转换酶（AST）、超氧物歧化酶（SOD）及谷胱甘肽过氧化物酶（GSH—Px）活力,丙二醛（MAD）及一氧化氮（NO）含量。结果人参皂苷Rb,及Rb：组合物5、10、20mg／kg均可明显缩小急性心肌梗死大鼠的MIS,降低血清CK、LDH、AST活性及MAD含量,提高血清SOD、GSH—Px活性及NO含量。结论人参皂苷Rb,及Rb：组合物对大鼠急性心肌梗死具有明显保护作用,可能与其增强抗氧化酶活性,减少氧自由基对心肌的损伤等机制有关。     

Ecklonia cava Polyphenol Has a Protective Effect against Ethanol-Induced Liver Injury in a Cyclic AMP-Dependent Manner

Previously, we showed that Ecklonia cava polyphenol (ECP) treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS) and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0–24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1) expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner.     

Protective Effects of Marine Alkaloid Neolamellarin A Derivatives against Glutamate Induced PC12 Cell Apoptosis

Marine alkaloids obtained from sponges possess a variety of biological activities and potential medicinal value. The pyrrole-derived lamellarin-like alkaloids, especially their permethyl derivatives, show low cytotoxicity and potent MDR reversing activity. Neolamellarin A is a novel lamellarin-like alkaloid which was extracted from marine animal sponges. We reported the synthetic method of permethylated Neolamellarin A and its derivatives by a convergent strategy in 2015. In 2018, we reported the synthesis and the neuroprotective activity in PC12 cells of 3,4-bisaryl-N-alkylated permethylated Neolamellarin A derivatives. In this report, another series of 15 different 3,4-bisaryl-N-acylated permethylated Neolamellarin A derivatives were synthesized, and the outstanding protective effects of these compounds against glutamate induced PC12 cell apoptosis were presented and discussed. These Neolamellarin A derivatives which possessed low cytotoxicity and superior neuroprotective activity may have the potential to be developed into antagonists against glutamate induced nerve cell apoptosis.     

The Emerging Evidence for a Protective Role of Fucoidan from Laminaria japonica in Chronic Kidney Disease-Triggered Cognitive Dysfunction

This study aimed to explore the mechanism of fucoidan in chronic kidney disease (CKD)-triggered cognitive dysfunction. The adenine-induced ICR strain CKD mice model was applied, and RNA-Seq was performed for differential gene analysis between aged-CKD and normal mice. As a result, fucoidan (100 and 200 mg kg⁻¹) significantly reversed adenine-induced high expression of urea, uric acid in urine, and creatinine in serum, as well as the novel object recognition memory and spatial memory deficits. RNA sequencing analysis indicated that oxidative and inflammatory signaling were involved in adenine-induced kidney injury and cognitive dysfunction; furthermore, fucoidan inhibited oxidative stress via GSK3β-Nrf2-HO-1 signaling and ameliorated inflammatory response through regulation of microglia/macrophage polarization in the kidney and hippocampus of CKD mice. Additionally, we clarified six hallmarks in the hippocampus and four in the kidney, which were correlated with CKD-triggered cognitive dysfunction. This study provides a theoretical basis for the application of fucoidan in the treatment of CKD-triggered memory deficits.     

Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

The frequent occurrence of Moorea producens (formerly Lyngbya majuscula) blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC₅₀ value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH) efflux, nuclear condensation and caspase-3 activity with EC₅₀ values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria.     

Design and Synthesis of Novel Xyloketal Derivatives and Their Protective Activities against H2O2-Induced HUVEC Injury

In this work, we designed and synthesized a series of amide derivatives (1–13), benzoxazine derivatives (16–28) and amino derivatives (29–30) from xyloketal B. All 28 new derivatives and seven known compounds (14, 15, 31–35) were evaluated for their protection against H₂O₂-induced HUVEC injury. 23 and 24 exhibited more potential protective activities than other derivatives; and the EC₅₀ values of them and the leading compound 31 (xyloketal B) were 5.10, 3.59 and 15.97 μM, respectively. Meanwhile, a comparative molecular similarity indices analysis (CoMSIA) was constructed to explain the structural activity relationship of these xyloketal derivatives. This 3D QSAR model from CoMSIA suggested that the derived model exhibited good predictive ability in the external test-set validation. Derivative 24 fit well with the COMSIA map, therefore it possessed the highest activity of all compounds. Compounds 23, 24 and 31 (xyloketal B) were further to examine in the JC-1 mitochondrial membrane potential (MMP) assay of HUVECs using flow cytometry (FCM). The result indicated that 23 and 24 significantly inhibited H₂O₂-induced decrease of the cell mitochondrial membrane potential (ΔΨm) at 25 μM. Collectively, the protective effects of xyloketals on H₂O₂-induced endothelial cells may be generated from oxidation action by restraining ROS and reducing the MMP.     

Traumatic Brain Injury Has Not Prominent Effects on Cardiopulmonary Indices of Rat after 24 Hours: Hemodynamic,Histopathology, and Biochemical Evidence

Background: Accidents are the second reason for mortality and morbidity in Iran. Among them, brain injuries are the most important damage. Clarification of the effects of brain injuries on different body systems will help physicians to prioritize their treatment strategies. In this study, the effect of pure brain trauma on the cardiovascular system and lungs 24 hours post trauma was assessed. Methods: Male Wistar rats (n = 32) were divided into sham control and traumatic brain injury (TBI) groups. In TBI animals, under deep anesthesia, a blow to the head was induced by the fall of a 450 g weight from 2 m height. Twenty four hours later, heart electrocardiogram and functional indices, cardiac troponin I, IL-6, TNF-, IL-Iβ in tissue and serum, and the histopathology of heart and lung were assessed. Results: The results showed that none of the functional, biochemical, inflammatory, and histopathology indices was statistically different between the two groups at 24 hours post TBI. Indices of impulse conduction velocity in atrium (P wave duration and P-R interval) were significantly longer in the TBI group. Conclusion: Overall, no important functional and histopathologic disturbances were found in heart and lung of TBI group after 24 hours. If the data is reproduced in human studies, the medical team could allocate their priority to treatment of brain disorders of the victim in the first 24 hours of pure TBI and postpone extensive assessment of heart and lung health indices to later time, thus reducing patient and health system expenditures. Key Words: Brain injury (TBI), Cardiopulmonary, Myocardial contraction, Cytokines     

茶树花对大鼠致畸作用的研究

为研究茶树花对SD大鼠母体及胎仔的致畸毒性,将交配成功的SD孕鼠随机分为4组,每组至少12只。设供试茶树花提取物0．50、1．00、2．00g／kg三个剂量组及阴性对照组,分别在妊娠的7～16天灌胃给予。妊娠期间记录孕鼠体重,于妊娠第20天断头处死孕鼠,记录着床数、活胎数、死胎数和吸收胎数;检查胎鼠外观、内脏和骨骼,并称胎鼠体重,量体长。结果显示,除低剂量组（0．50g／kg）胎鼠体长显著高于对照组外（P〈0．01）,其余剂量组对孕鼠和胎鼠的各项毒效应观察指标与对照组相比均无显著差异。表明在本试验条件下,茶树花对孕鼠生长和胚胎发育无不良影响和致畸作用。     

A Historic Review of the Role of CD4+ T-Cell Subsets in Development of the Immune Responses against Cutaneous and Visceral Leishmaniases

The heterogeneity of CD4⁺ T cells has been investigated since the late 1970s, when their Th1 and Th2 subsets were coined. Later studies on the cutaneous form of the Leishmaniasis were focused on the experimental models of Leishmania major infection using the susceptible BALB/c and the resistant C57BL/6 mice. At the early 21^st century, the T_reg subpopulation was introduced and its role in concomitant immunity, responsible for lifelong resistance of the host to the reinfection was proposed. Subsequent studies, mainly focused on the visceral form of the infection pointed to the role of IL-17, produced by Th17 subset of CD4⁺ T cells that along the neutrophils were shown to have important yet equivocal functions in protection against or exacerbation of the infection. Altogether, the current knowledge indicates that the above four subsets could orchestrate the immune, the regulatory and the inflammatory responses of the host against different forms of leishmaniases. Key Words: Immunity, Leishmaniasis, T-Lymphocytes