Congestive Heart Failure: Treatment of Symptoms or Causes

This paper is based on the author’s 20+ years of experience treating patients with congestive heart failure (CHF) as a cardiologist. In the 20+ years, 64 patients were treated, including both with reduced and preserved left ventricular function. Most patients had a 4 - 5 days hospitalization in their first admission with one readmission (1.6%) over seven years. This paper will help us understand the physiology and pathophysiology of congestive heart failure, especially how to use beta blockers and diuretics. It will shorten the length of hospitalization and lower the readmission rate and cost of CHF treatment. This paper will help us to open another research direction for CHF.

Point-of-care ultrasound in diagnosis and management of congestive nephropathy

Congestive nephropathy is kidney dysfunction caused by the impact of elevated venous pressures on renal hemodynamics.As a part of cardiorenal syndrome,the diagnosis is usually made based on history and physical examination,with findings such as jugular venous distension,a third heart sound,and vital signs as supporting findings.More recently,however,these once though objective measures have come under scrutiny for their accuracy.At the same time,bedside ultrasound has increased in popularity and is routinely being used by clinicians to take some of the guess work out of making the diagnosis of volume overload and venous congestion.In this mini-review,we will discuss some of the traditional methods used to measure venous congestion,describe the role of point-of-care ultrasound and how it can ameliorate a clinician’s evaluation,and offer a description of venous excess ultrasound score,a relatively novel scoring technique used to objectively quantify congestion.While there is a paucity of published large scale clinical trials evaluating the potential benefit of ultrasonography in venous congestion compared to gold standard invasive measurements,more study is underway to solidify the role of this objective measure in daily clinical practice.

SERUM CONCENTRATIONS OF HYALURONIC ACID, PROCOLLAGEN TYPE III NH_2-TERMINAL PEPTIDE, AND LAMININ IN PATIENTS WITH CHRONIC CONGESTIVE HEART FAILURE

Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chronic congestive heart failure （CHF）. Methods Serum levels of HA, PCIIIP, and LN in 39 patients with CHF E [14 with New York Heart Association （NYHA） functional class II, 21 with class Ⅲ, 4 with class Ⅳ] and in 46 patients with NYHA functional class I were assessed by radioimmunoassay. Results The serum concentrations of HA, PCMP, and LN were 359.75 ± 84.59 μg/L, 77.88 ± 24. 67 μg/L, 86. 73 ± 23.90 μg/L in CHF group, and 211.60 ±54. 80 μg/L, 64.82 ±23.99 μg/L, 82. 26 ±23.98 μg/L in NYHA functional class Ⅰ group, respectively. The HA level was significantly higher in CHF patients as compared with NYHA functional class Ⅰ group （ P 〈 0.05 ）. However, no difference was found in the levels of PCIIIP and LN between CHF group and NYHA functional class Ⅰ group. The serum HA concentration was negatively correlated with left ventricular ejection fraction （ r = - 0.71, P 〈 0.05 ）. Conclusion Serum HA level may act as an indicator for myocardial fibrosis.

Review:Cell therapy in congestive heart failure

Congestive heart failure （CHF） has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout （necrosis and apoptosis） plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells （CSCs） within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells （BMCs） to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animat CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction.

Safety and predictors of adherence of a new rehabilitation program for older women with congestive heart failure

Objectives To assess the safety of a cardiac rehabilitation program for older women with Congestive Heart Failure （CHF） and determine if certain factors influence adherence. Methods Women over the age of 65 with CHF attended an exercise program supervised by a physiotherapist. Quality of life was measured by the Minnesota Living with Heart Failure Questionnaire （MLHFQ） and severity of disease by the New York Heart Association （NYHA） Class. Subjects were classified into those who attended 90% or more of the sessions and those who attended less than 90% of the sessions. Results Fifty-one subjects were studied. Eight subjects did not attend any sessions. Of the 43 attendees, the average percentage of sessions attended was 87%. There were no significant differences between the two groups in age, MLHFQ or NYHA Class. There was only one adverse event out of 280 participant attendances. Conclusions The program had a high level of adherence in this population. Age, MLHFQ or NYHA Class did not impact on session attendance. Our data suggests this program is safe for this population. Further research is needed to determine other predictors of attendance and the examination of safety issues and long-term adherence to exercise in this population.

Study on Apoptosis and Expression of P53, Bcl-2,Bax in Cardiac Myocytys of Congestive Heart Failure Induced by Ventricular Pacing

The apoptosis and the expression of p53, bcl-2 and Bax in myocytes of chronic rapid ventricular pacing-induced congestive heart failure (CHF) in rabbits were investigated. The CHF rabbit model (P, n=7) was established by chronic rapid ventricular pacing for 3 weeks. By using TUNEL technique the apoptosis in the myocytes in the rabbit model was studied and the expression of p53, bcl-2 and Bax in myocytes was detected by using immunohistochemical method. Sham-operated (C, n=9) group served as control group. The results showed that there were about 4033± 884.56 apoptotic cells/10 6 myocytes in P group, but no apoptotic cells were found in C group. Myocytes positive for p53 immunoreactivity (18.86±8.48 vs 5.06±0.87, P<0.01) and positive for Bax immunoreactivity (7.15±1.91 vs 0.43±0.09, P<0.01) were increased in P group as compared with those in C group, while the myocytes positive for bcl-2 immunoreactivity (7.08±1.05 vs 14.97±4.47, P<0.01) and the ratio of bcl-2/Bax were decreased in P group as compared with those in C group. Apoptosis was involved in the development of CHF induced by continuously rapid ventricular pacing in rabbit. The expression of p53 and Bax was increased, while the expression of bcl-2 was inhibited. These might play an important role in the acceleration of the apoptosis.

Correlation between Serum Uric Acid Level and Left Ventricular Ejection Fraction in Patients with Congestive Heart Failure

Background: One of the risk factors of congestive heart failure that still under investigations is hyperuricemia. It’s still debatable whether it’s an independent risk factor or it’s just a consequence of other disorders associated with cardiovascular diseases like hypertension, diabetes and dyslipidemia. Objective: The aim of our study is to elucidate whether in patients with heart failure serum uric acid level correlates with left ventricular ejection fraction supporting the possibility that the detection of progressive hyperuricemia in these patients may be an indicator of deteriorating cardiac function. Methods: We conducted a prospective study that included 124 studied patients and 26 apparently healthy persons at Coronary care unit and Internal Medicine Department at Sohag University Hospitals. Studied populations were classified into;* Group “I”: newly diagnosed heart failure, * Group “II”: decompensated heart failure on regular treatment, * Group “III”: decompensated heart failure but stopped their treatment from three months, Group “IV”: control group, healthy and age-matched subjects. We studied the association between left ventricular ejection fraction, the severity of congestive heart failure and the serum uric acid levels and the well-known conventional risk factors. Results: The main finding was the significantly higher mean serum uric acid levels in patients with congestive heart failure versus apparently healthy persons with “P value = 0.02”. When we adjusted the serum uric acid with other significant risk factors in the univariate analysis which were age, gender and smoking, serum uric acid was an independent risk factor “P value = 0.04”. There was a significant correlation between serum uric acid level and the severity of congestive heart failure “P value 0.35”. High rates of serum uric acid levels were recorded in patients with reduced ejection fraction. A uric acid level of 8.45 mg/dl was found to be the most appropriate cut-off point with the sensitivity 62% and the specificity 78.5%. Conclusion: Higher serum uric acid levels are significantly correlated with the severity of congestive heart failure and left ventricular ejection fraction. Serum uric acid is an independent risk factor for congestive heart failure.

Clinical Study on Chronopharmacokinetics of Digoxin in Patients with Congestive Heart Failure

Fluorescence polarization immunoassay was used to study the chronopharmacokirietics of digoxin in 10 patients with congestive heart failure (CHF) who also served as self-controls. Our results showed that the serum digoxin concentration reached peak value 1h after taking digoxin at 7: 00 a. m.,but the serum digoxin concentration reached the peak value 2 h after taking digoxin at 4: 00 p. m.. The average serum digoxin concentration area under curve was greater and the best maintainable time of serum concentration within 24 h after taking digoxin at 4 p. m. longer than those at 7: 00 a. m.. The heart rates were obviously lower and the cardiac function was significantly improved in 4:00 p. m.group.

Clinical study of recombinant human brain natriuretic peptide in patients with acute myocardial infarction complicating congestive heart failure

Objectives To observe the efficacy and safety of recombinant human brain natriuretic peptide(rh-BNP) on patients with acute myocardial infarction complicating congestive heart failure.Methods 40 patients with acute myocardial infarction complicated by congestive heart failure were randomly divided into control group and treatment group of 20 cases.The control group,15 cases of acute anterior myocardial infarction,5 cases of acute inferior wall myocardial infarction, 15 males and 5 females,aged 55-70 years,mean age 58±12 years;treated 16 cases of acute anterior myocardial infarction,4 cases of acute myocardial infarction,16 males and 4 females,aged 56-70 years,mean age 59±11 years;two groups of age,gender,severity of disease and vascular lesions no significant difference and comparable(P】0.05).Conventional group were given aspirin,clopidogrel, statins,Inotropic,diuretic and vasodilator therapy.In the con- ventional treatment group based on the use of recombinant human brain natriuretic peptide(new bios,Tibet Pharmaceutical Co.,Ltd.Chengdu Nuodikang biopharmaceutical production, usage:1.5μg/Kg intravenous injection(impact), then 0.0075μg-0.01μg/(kg·min)infusion rate).Continuous medication 72 h.The clinical symptoms observed for 3 days in patients before treatment and after treatment,heart rate,blood pressure and left ventricular ejection fraction (LVEF) and tumor necrosis factor(TNF-α),brain natriuretic peptide(BNP) levels were measured.Results In control group,8 cases markedly effect,5 cases effect and 7 cases no effect,the total effective rate was 65%;In treatment group,13 cases markedly effect,6 cases effect and 1 cases no effect,the total effective rate was 95%,compared with two groups P New bios treatment group significantly increased cardiac index(CI) in patients with heart failure and left ventricular ejection fraction(LVEF) than the control group(all P【0.05),further reduce the levels of tumor necrosis (TNF-α) and brain natriuretic peptide(BNP).Conclusions rh-BNP can improve symptoms and heart function,reduced plasma tumor necrosis factor(TNF-α) and BNP levels of acute myocardial infarction patients with congestive heart failure,the treatment safe and reliable.As small sample size observed,larger sample to be accumulated to further evaluate its efficacy and safety.

Clinical Study on Effect of Shenmai Injection in Treating Congestive Heart Failure

Objective: To observe the therapeutic effect of Shenmai Injection (SI) in treating congestive heart failure (CHF). Methods: The changes in cAMP, cGMP, serum cardiac troponin T (cTnT, a specific marker reflecting myocardial injury), creatine kinase (CK) and creatine kinase isoenzyme (CK-

Effectiveness of Bumetanide Infusion in Treatment of Generalized Edema and Congestive Heart Failure

Generalized edema (anasarca) is common in nephrotic syndrome which rarely produces shortness of breath. Increased shortness of breath associated with rapid weight gain and generalized edema signify congestive heart failure (CHF). Loop diuretics consisting of furosemide (Lasix&#174), bumetanide (Bumex&#174), torsemide (Demadex&#174) or ethacrynic acid (Edecrin) are effective diuretics to treat anasarca. However, efficacy varies depending on the renal function. Loop diuretic given orally or by intravenous boluses produce good urine output but overall response in reducing edema or shortness of breath as in CHF is less than optimum. Although literature information is very limited, continuous bumetanide infusion for 72 to 96 hours is found to be very effective in producing subjective relief of shortness of breath as well as objective improvement such as reduction in brain natriuretic peptide in CHF and improved kidney function, so that diuresis is sustained even after discontinuation of the infusion. Decrease in kidney function and electrolytes and acid-base imbalance are common but they are reversible with prompt replacement therapy. They pose no threat to life.

Echocardiographic Evaluation of Cardiac Dyssynchrony in Patients with Congestive Heart Failure

The present study investigated the application of echocardiography to evaluation of cardiac dyssynchrony in patients with congestive heart failure（CHF）. A total of 348 consecutive CHF patients who were admitted for cardiac resynchronization（CRT） and presented with low ejection fraction（EF） and wide QRS duration were enrolled in this study, along with 388 healthy individuals. Dyssynchrony was assessed based on filling time ratio（FT/RR）, left ventricular pre-ejection delay（PED）, interventricular mechanical delay（IVMD）, longitudinal opposing wall delay（LOWD） and radial septal to posterior wall delay（RSPWD）. Response to CRT was defined as a ≥15% increase in EF. The results showed that FT/RR was decreased while PED, IVMD, LOWD and RSPWD were increased in the CHF group compared with the control group（P〈0.01）. In the CHF group, FT/RR was negatively correlated with the QRS duration, LV end-diastolic diameter（LVESd）, LV end-diastolic volume（LVEDV） and LV end-systolic volume（LVESV）（P〈0.01）, but positively with the LVEF（P〈0.01）. Additionally, PED, IVMD, LOWD and RSPWD were positively correlated with the QRS duration, LVESd, LVEDV and LVESV（P〈0.01）, but negatively with the LVEF（P〈0.01）. The CHF group was divided into three subgroups according to the varying degrees of LVEF. FT/RR decreased successively from the LVEF-1 group to the LVEF-2 group to the LVEF-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order（P〈0.01）. The CHF group was divided into three subgroups according to the varying degrees of QRS duration, and FT/RR decreased successively in a sequence from the QRS-1 group to the QRS-2 group to the QRS-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order（P〈0.01）. Speckle tracking radial dyssynchrony ≥130 ms was predictive of an EF response in patients in QRS-1 group（78% sensitivity, 83% specificity）, those in QRS-2 group（83% sensitivity, 77% specificity） and in QRS-3 group（89% sensitivity, 79% specificity）. In conclusion, echocardiography is a convenient and sensitive method for evaluating cardiac dyssynchrony in patients with CHF.

Relationship Between Serum Leptin Concentration and Lipids & Body Mass Index in Patients With Chronic Congestive Heart Failure

Objectives To investigate the relationship of serum leptin concentration with the lipids and body mass index （BMI） in patients with chronic congestive heart failure（CHF）. Methods The serum concentration of leptin in 39 patients with CHF （14 in cardiac function class Ⅱ , 21 in class Ⅲ, 4 in classⅣ , NYHA） and in 46 patients with cardiac function class Ⅰ （NYHA） were assessed by radioimmunoassay. Results The serum concentration of leptin were 9.018±4.519 μg/l in CHF group （cardiac function class Ⅱ 11.492±5.649 μg/l, class Ⅲ 7.763±3.321 μg/l, class Ⅳ 6.100±2.657 μg/l）; 11.674± 6.911 μg/l in class Ⅰ group. The serum concentrations of leptin were significantly lower in CHF group, as compared with class Ⅰ group （P〈 0.05）. Moreover, the decrease of serum leptin concentration was significantly correlated with the decreased serum concentrations of total cholesterol, triglyceride, body mass index and left ventricular ejection fraction in CHF group, respectively （P 〈 0.05）. Conclusions The significance of the decrease in serum leptin in CHF patients needs further study.

A hospital based study on causes peculiar of congestive cardiac failure(CCF)

Objective:To determine the frequency of risk factors of congestive cardiac failure in a tertiary care hospital of Peshawar.Methods:This retrospective observational study was conducted in department of Cardiology,Postgraduate Medical Institute,Lady Reading Hospital Peshawar,from March 2005 to September 2007.Relevant information regarding the risk factors of congestive cardiac failure were recorded on questionnaire prepared in accordance with the objectives of the study.Results:1 019 patients with established diagnosis of cardiac failure (based on clinical findings and relevant investigations) were included.Out of total sampling 583 (57.12%) were males and 436(42.78%) were females.The age range of the patients was from 6 years to 82 years with mean age of 48.5 years and mode of age was 45 years.The distribution of causative factors of CCF was:ischemic heart disease(IHD) 36.31%,hypertension 26.30%,dilated cardiomyopathy 10.10%,obstructve and restrictive cardiomyopathies 5.39%,valvular heart diseases(VHD) 9.32%,congenital heart disease like ventricular septal defects(VSD) 4.41%,atrial septal defects(ASD) 0.58%,atrial fibrillation (AF) 2.25%,constrictive pericardidtis 1.07%.Pericardial effusion 0.68%,chronic obstructive pulmonary disease and pulmonary hypertension 1.47%,thyrotoxicosis 0.68%,complete heart block 0.29%and paget disease in 0.09%cases.Conclusion:Ischemic heart disease,hypertension,cardiomypathies,valvular heart disease and congenital heart disease are major contributor to CCF in our patients.

Congestive Heart Failure Clinics:How to Make Them Work in a Community-Based Hospital System

Introduction:Congestive heart failure(CHF)accounts for over$32 billion in health care costs per year and is at the epicenter of health care reform.CHF remains a major cause of hospitalizations.It is known and has been reported that missed diagnosis of and missed opportunities to treat heart failure are associated with higher mortality and morbidity.CHF disease management programs have emerged as a potential solution to the CHF epidemic.The paradox remains that CHF disease management programs still cluster in tertiary hospital systems.The impact of heart failure specialists and specialty teams in community health systems is less well understood.Currently there are not enough CHF-trained teams in the community setting to address this unmet health need.Methods:We explored the impact of CHF clinics in a community-based hospital system on readmission rates,mortality,and symptomatic relief.A total of 384 patients were enrolled in the clinic between 2012 and 2015.Data collected included age,sex,type of heart failure,New York Heart Association class,ejection fraction,serum creatinine and brain natriuretic peptide values,and readmission and mortality rates within 30 days,3 months,6 months,and 1 year.We also compared readmission rates between patients who were followed up in the CHF clinic versus those who were not seen in the CHF clinic.Results:A statistically signifi cant difference was demonstrated in readmission rates between patients who were followed up in the CHF clinic versus those who did not visit the CHF clinic for up to 1 year of follow-up.Conclusion:CHF community hospital clinics that use a rapid and frequent follow-up format with CHF-trained teams effectively reduce rehospitalization rates up to 1 year.

Relationship of Intralymphocytic Cyclic Nucleotide and Calcium Ion Changes with Cardiac Function in Congestive Heart Failure Patients Treated with Amrinone

The contents of intralymphocytic cyclic nucleotide（cAMP and cGMP）and cal-cium ions(Ca++)were determined in 20 patients with refractory congestive heart failure be-fore and after the treatment of Chinese-made amrinone,and their cardiac index was alsomcasured with the thermodilution technique.It was found that the cAMP andCa++contents were markedly elevated while the cardiac index increased under amrinonctreatment,and that both the cAMP and Cacontents were in positive correlation withthe cardiac index before and after amrinone administration.It is suggested that amrinone is likcly to exert its positive inotropic effect on themyocardium through augmenting the cAMP and Ca++contents in myocardial cells,andthat the determination of intralymphocytic cyclic nuclcotidc and Ca++might bc of signifi-canoe to assess the impairment of cardiac function and the cfficacy of a thcrapcuticagent.

Improved Cardiac Contractility of Human Recombinant Growth Hormone on the Congestive Heart Failure of Pig

The enhanced cardiac contractility effect of human recombinant growth hormone (hr-GH) on the congestive heart failure (CHF) was studied on the pig. To build a pig model of congestive heart failure, a temporary artificial cardiac pacemaker was implanted in the pig’s body and paced at 220 beats to 240 beats per minute for 1 week. After the model of congestive heart failure was successfully set up, the frequency of the pacemaker was changed to 150 beats to 180 beats per minute to maintain the CHF model stable. Pigs were divided into three groups: The hr-GH group in which 0.5 mg/kg per day of hr-GH was administrated intramuscularly for 15 days, the injection control group in which an equal amount of physiological saline was injected intramuscularly, and a normal control group. The left ventricular diastolic end pressure was (10.60±2.41) mmHg in the hr-GH group, but (19.00±3.81) mmHg in the saline control group (P<0.01); Cardiac output was (1.86±0.13) L/min in the hr-GH group, but (1.56±0.18) L/min in the saline control group (P<0.05); Peripheral vascular resistance was (56.88±7.51) mmHg·(L/min) -1 in the hr-GH group, whereas (70.30±11.59) mmHg·(L/min) -1 in the saline control group (P<0.05); +dp/dt max was (2900±316.23) and (2280±286.36) in the hr-HG group and the saline control group respectively (P<0.05). The results show that hr-GH enhances myocardial contractility of CHF, and the CHF model built by a temporary artificial cardiac pacemaker at a high rate of stimulation is reasonable and applicable.

Congestive heart failure masquerading as acute abdomen:A case report

Rationale:As an uncommon manifestation of congestive heart failure,congestive hepatopathy requires an early diagnosis in order to render appropriate care.Misdiagnosis as intraabdominal sepsis may lead to erroneous initial intervention,such as fluid boluses,that can potentially tip an already sick patient with poor reserves over into an extreme state.Patient’s Concern:A 65-year-old man was brought to the emergency department for excruciating abdominal pain,vomiting and jaundice.He also had lower limb pitting edema and was hypotensive en route.Diagnosis:Congestive hepatopathy.Interventions:Intravenous furosemide and fluid restriction.Outcomes:The patient declined admission to the cardiology ward and discharged himself against medical advice after his condition was improved in the emergency department.Lessons:It is important to pay attention to acute abdominal pain induced by extraabdominal pathologies.In this case of acute decompensated congestive heart failure,early recognition of the cause makes a difference to the management.

Reversible congestive heart failure associated with hypocalcemia:A case report

BACKGROUND Hypoparathyroidism is a rare disease that may occur due to primary or secondary etiologies.The estimated incidence in the United States is 24–37/100000 personyears.Congestive heart failure associated with hypocalcemia due to hypoparathyroidism is an even rarer presentation.CASE SUMMARY Here,we present a 64-year-old woman with congestive heart failure following hypocalcemia.The patient was transferred to our emergency department with complaints of rapidly progressive dyspnea,shortness of breath and heaviness of the chest for 4 d.She had a history of undergoing thyroidectomy and partial tracheotomy 2 years prior due to a malignant thyroid tumor.Muscle spasms had been present 1 year ago,and cataracts were treated with intraocular lens replacement in both eyes.Most tests were within normal ranges,except serum calcium at 1.33 mmol/L(2.20–2.65 mmol/L),ionized calcium at 0.69 mmol/L(1.15–1.29 mmol/L),and parathyroid hormone at<1.0 pg/mL(12–88 pg/mL).Echocardiography revealed an ejection fraction of 28.48%.Cardiac function was quickly reversed by restoring the serum calcium concentration.Significant improvements were noted with an ejection fraction of up to 48.50%at follow-up.CONCLUSION For patients with potential hypocalcemia,monitoring calcium levels and dealing with hypocalcemia in time to avoid serious complications are important.

Intervention Effect of Jianxin Decoction (健心汤) on Serum Cytokine Level of Congestive Heart Failure Patients

Objective: To investigate the intervention effect of Jianxin Decoction (健心汤, JXD) on the cytokine level in serum of patients with congestive heart failure (CHF). Methods; Sixty-six patients with CHF were randomly divided into the control group (n = 33) and the trial group (n = 33). The control group received conventional treatment, and the trial group was treated with conventional therapy plus JXD for 4 weeks. Before and after treatment, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitrogen monoxide (NO) in serum and cardiac function were determined. Results: After treatment, the levels of TNF-α, IL-6 and NO were significantly lower than those before treatment (P<0.05, or P<0.01) in the two groups, and the lowering degree of the indices in the trial group was more significantly reduced than that in the control group (P<0.05). And cardiac functions in both groups were improved significantly (P<0.05, or P< 0.01). Conclusion: JXD could prevent and reverse ventricular remodeling so as to ameliorate cardiac function through regulating the levels of cytokines.