ABSTRACT
Diabetes mellitus is a chronic condition defined by elevated blood sugar levels (hyperglycemia). This condition can lead to complications such as nephropathy, which is histologically shown with glomerulosclerosis. Glucomannan, a component of Amorphophallus muelleri, offers numerous health benefits, but its direct therapeutic effect on glomeruli remains uncertain. Male Wistar rats which were taken with random sampling (n = 30) were distributed into six distinct groups. All groups, excluding Group N, received 125 mg/kg BW single intraperitoneal dose of alloxan. Group N received a single dose of PBS 125 mg/kg BW. After 7 days, Group K + was induced with acarbose at a dose of 50 mg/70 kg BW (adjusted using a factor of 0.018) orally per day. Groups N and K - induced with 1% CMC Na at 0.2 mL/0.1 kg orally per day. While Group P1, P2, and P3 were orally given A. muelleri ethanolic extract orally per day at a dose of 100, 200, and 400 mg/kg BW. The following 50 days of treatment, the Wistar rats were euthanized, and their kidney was preserved for histological slides that were stained with hematoxylin and eosin. The oral administration of A. muelleri ethanolic extract in alloxan-induced diabetic rats led to a significant decrease in the average of glomerulosclerosis instances when compared to the K - group. The most effective dose was observed at 400 mg/kg BW per day. A. muelleri administration leads to a reduction in glomerulosclerosis occurrences, suggesting its potential as a therapeutic approach for reducing complications probability linked to hyperglycemia.
ABSTRACT
Background and aims: Meals with high protein and fiber could reduce weight and improve diabetes risk factors. Isomalto-oligosaccharide (IMO), a form of dietary fiber, could induce the afferent signal that causes appetite suppression. However, the direct effect of fiber supplementation in the form of IMO combined with a high-protein diet (HPF) on those parameters is still unknown. This study aims to investigate the effect of HPF on anthropometric parameters and blood glucose regulation of healthy subjects. . Methods: Thirteen healthy subjects were given a hypocaloric high protein diet (HPD) mixed with their prepared meals for two weeks. Followed by the HPF diet for another two weeks. Their anthropometric parameters, such as body composition (total body weight, body fat percentage, and fat-free mass), BMI and waist circumference, and fasting plasma glucose, were measured. Results: Compared to pre-intervention, HPF could significantly (p ≤ 0.004) reduce the anthropometric parameters and fasting plasma glucose. Compared to HPD, HPF could significantly (p ≤ 0.005) reduce more total body weight, body fat percentage, and BMI. In addition, HPF could induce more satiety than HPD (higher VAS score). Conclusion: HPF could improve the subject's anthropometric parameters which is obviously beneficial in preventing the risk of developing diabetes.
ABSTRACT
Introduction: C-C chemokine receptor-2 (CCR-2) and C-C chemokine ligand-5 (CCL-5) play an important role in the migration of monocytes, macrophages, dendritic cells, and activated T cells against Mycobacterium tuberculosis (M.tb). Meanwhile, signal transducer and activator of transcription 3 (STAT-3) and suppressor of cytokine signaling 3 (SOCS-3), activated by interleukin (IL)-6 and IL-10 in tuberculosis (TB) infection, play an important role in phagocytosis, inflammation, and granulomatous-forming processes that may lead to TB treatment success or failure. However, there are no data about the expression of those markers in tuberculous lymphadenitis. The characterization of those markers is very critical to put a fundamental basis to understand the homing mechanism of tuberculous lymphadenitis. Aim of study: The specific objective of this study is to characterize the expression pattern of CCR-2-CCL-5, IL-6, IL-10, STAT-3, and SOCS-3 in tuberculous lymphadenitis. Methods: The study was performed on 27 cases of tuberculous lymphadenitis node biopsies. The diagnosis of tuberculous lymphadenitis was based on the clinical criteria and the presence of the histological feature characteristic of TB granulomas. Afterward, immunohistochemistry was stained with CCR-2, CCL-5, IL-6, IL-10, STAT-3, and SOCS-3. A semiquantitative analysis of IHC images was performed to examine protein expression in stained preparations. The expression was also manually counted. Results: Compared with the normal area, both lymphocytes and macrophages expressed strongly CCR-2-, CCL-5, and IL-6, while IL-10, STAT-3-, and SOCS-3- were expressed lowly. There was a strong positive correlation between CCR-2 with IL-6 (p = 0,83) and IL-10 (p = 0,83). Conclusion: The chronic infection process of tuberculous lymphadenitis was characterized by the expression of IL-10low, STAT-3low, SOCS-3low, CCR-2high, CCL-5high, and IL-6high. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT05202548.
Subject(s)
Latent Tuberculosis , Tuberculosis, Lymph Node , Humans , Chemokines , Cytokines , Interleukin-10 , Interleukin-6 , Receptors, Chemokine , Suppressor of Cytokine Signaling Proteins/geneticsABSTRACT
BACKGROUND: Tuberculosis (TB) remains one of the highest Asia's health problems. Spondylitis TB in diabetes mellitus (DM) and hypothyroidism patients is a rare case of extrapulmonary tuberculosis. However, there is a lack of therapeutic guidelines to treat spondylitis TB, particularly with type 2 DM (T2DM) and hypothyroidism as comorbidities. Here we present a case of spondylitis TB with T2DM and hypothyroidism in a relatively young patient and its therapeutic procedure. CASE SUMMARY: We report the case of a 35-year-old male patient from Surabaya, Indonesia. Based on anamnesis, physical examination, and magnetic resonance imaging, the patient has been categorized in stage II of spondylitis TB with grade 1 paraplegia. Surprisingly, the patient also had a high HbA1c level, high thyroid stimulating hormone, and low free T4 (FT4), which indicated T2DM and hypothyroidism. A granulomatous process was observed in the histopathological section. The antituberculosis drugs isoniazid and rifampicin were given. In addition, insulin, empagliflozin, and linagliptin were given to control hyperglycemia conditions, and also levothyroxine to control hypothyroidism. CONCLUSION: The outcome was satisfactory. The patient was able to do daily activities without pain and maintained normal glycemic and thyroid levels. For such cases, we recommend the treatment of spondylitis TB by spinal surgery, together with T2DM and hypothyroidism therapies, to improve the patients' condition. Prompt early and non-invasive diagnoses and therapy are necessary.
ABSTRACT
A unique glycoprotein is expressed on the virus envelope of human herpesvirus 6B (HHV-6B): the complex gH/gL/gQ1/gQ2 (hereafter referred to as the HHV-6B tetramer). This tetramer recognizes a host receptor expressed on activated T cells: human CD134 (hCD134). This interaction is essential for HHV-6B entry into the susceptible cells and is a determinant for HHV-6B cell tropism. The structural mechanisms underlying this unique interaction were unknown. Herein we solved the interactions between the HHV-6B tetramer and the receptor by using their neutralizing antibodies in molecular and structural analyses. A surface plasmon resonance analysis revealed fast dissociation/association between the tetramer and hCD134, although the affinity was high (KD = 18 nM) and comparable to those for the neutralizing antibodies (anti-gQ1: 17 nM, anti-gH: 2.7 nM). A competition assay demonstrated that the anti-gQ1 antibody competed with hCD134 in the HHV-6B tetramer binding whereas the anti-gH antibody did not, indicating the direct interaction of gQ1 and hCD134. A single-particle analysis by negative-staining electron microscopy revealed the tetramer's elongated shape with a gH/gL part and extra density corresponding to gQ1/gQ2. The anti-gQ1 antibody bound to the tip of the extra density, and anti-gH antibody bound to the putative gH/gL part. These results highlight the interaction of gQ1/gQ2 in the HHV-6B tetramer with hCD134, and they demonstrate common features among viral ligands of the betaherpesvirus subfamily from a macroscopic viewpoint.
Subject(s)
Herpesvirus 6, Human/metabolism , Receptors, OX40/metabolism , Roseolovirus Infections/metabolism , Viral Envelope Proteins/metabolism , HumansABSTRACT
Metformin is the most commonly prescribed drug for type 2 diabetes mellitus. Nowadays metformin is also use for efficacy in diabetes mellitus-tuberculosis coinfection patients through several mechanisms, such increasing superoxide production therefore activation isoniazid is increasing; inducing adeno-monophosphate kinase (AMPK) associated autophagy process; and regulating inflammation cytokines. This article will review the mechanism of action of Metformin as enhancer for anti tuberculosis efficacy.
Subject(s)
Antitubercular Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Antitubercular Agents/administration & dosage , Coinfection , Diabetes Mellitus, Type 2/complications , Drug Synergism , Drug Therapy, Combination , Humans , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Tuberculosis, Pulmonary/complicationsABSTRACT
Metformin (MET) is a potential combination drug to elevate anti-TB efficacy. However, the clinical effect, especially smear reversion, during metformin applied with anti-tuberculosis and insulin in patients with type 2 DM newly TB co-infection were remain unknown. An observational clinical study was done in DM newly TB co-infection outpatients at Surabaya Paru Hospital. This study evaluated MET therapy, at least 2 months, accompanying with insulin and anti-TB regimens and compared to comparison group. The smear, microtubule-associated Protein1 Light Chain 3B (MAP1LC3B) level, as the presentation of autophagy, Superoxide Dismutase (SOD) level, Interferon (IFN)-γ and Interleukin (IL)-10 levels were evaluated twice. From 42 participants in this study, 22 participants of observation group that received additional MET therapy, 100% had sputum smear reversion after 2-months intensive phase of anti-TB therapy. Whereas 25% of 20 participants of comparison group did not undergo reversion inserts sputum smear. As conclusion, MET has the potential of being an additive combination therapy to enhance the bactericidal effect of anti-TB on DM-TB coinfection patients. Metformin enhances the effects of anti-TB and insulin therapy in increasing the smear reversion by increasing autophagy.
Subject(s)
Antitubercular Agents/therapeutic use , Autophagy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Metformin/therapeutic use , Tuberculosis/drug therapy , Adult , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Drug Therapy, Combination , Ethambutol/therapeutic use , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Isoniazid/therapeutic use , Leukocytes, Mononuclear/metabolism , Microtubule-Associated Proteins/metabolism , Middle Aged , Pyrazinamide/therapeutic use , Rifampin/therapeutic use , Sputum/microbiology , Superoxide Dismutase/metabolism , Tuberculosis/complications , Tuberculosis/metabolismABSTRACT
IFN-γ elevation is one of the indicators of successful treatment in active tuberculosis (TB) infection due to macrophage and Th-1 activation in inducing autophagy process. However, IL-10 also inhibits interferon-mediated mycobactericid activities by blocking IFN-γ; signaling pathways in autophagy. Therefore, ratio IFN-γ/IL-10 has to be greater than 1 (>1) then IFN-γ remains has anti-mycobacterium. Metformin (MET) is a potent combination drug to elevate anti-TB efficacy and able to regulate inflammation. In this study, an observational clinical study was done in diabetes mellitus (DM)-TB co-infection outpatients at Surabaya Paru Hospital. This study evaluated how MET therapy; affected inflammation. MET was used at least 2 months, accompanying with insulin and; anti-TB and as comparison to non MET group. The result in this study MET increased both pro-inflammatory and anti-inflammatory cytokines, thus MET may consider as adjunct therapy in DM-TB coinfection patients due; to its ability in Th-1 and Th-2 immuno-regulating response, especially to enhance IFN-γ; and to reduce insulin associated IL-10 upregulation.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Interleukin-10/blood , Metformin/therapeutic use , Tuberculosis, Pulmonary , Adult , Female , Humans , Hypoglycemic Agents/pharmacology , Inflammation , Male , Metformin/pharmacology , Middle Aged , OutpatientsABSTRACT
Metformin (MET) has possibilities to be utilized as an adjunct of tuberculosis (TB) therapy for controlling the growth of Mycobacterium tuberculosis (M. tuberculosis). MET enhances the production of mitochondrial reactive oxygen species and facilitates phagosome-lysosome fusion; those mechanism are important in M. tuberculosis elimination. Moreover, MET-associated lactic acidosis (MALA) needs to be considered and the incidence of MALA in patients with type 2 DM-TB coinfection remains unknown. This result contributes much to our understanding about the clinical effect of MET use in type 2 DM-TB coinfection. For the purpose of understanding the MET effect as an adjuvant therapy in TB therapy and insulin simultaneous therapy, an observational clinical study was done in type 2 DM newly TB coinfection outpatients at Surabaya Paru Hospital. Patients were divided into two groups. First group was MET group, in which the patients were given MET accompanying insulin and TB treatment regimens, the golden standard therapy of DM-TB coinfection. MET therapy was given for at least 2 months. Second group was non-MET group, in which the patients were given insulin and TB treatment regimens. The lactate levels in both groups were measured after 2 months. Among 42 participants, there was no case of lactic acidosis during this study period. Data were normally distributed; thus, we continued analysis of the difference using paired T-test with 95% confidence. There was no difference in lactate levels (p=0.396) after MET therapy compared to non-MET group. In this study involving patients with TB pulmonary diseases, there is neither evidence that MET therapy induced lactic acidosis event nor that it increased lactate blood level. Thus, we concluded that MET use in type 2 DM-TB coinfection did not induce lactic acidosis.